[An analysis of the etiology composition and clinical characteristics of bilateral optic disc swelling].

Objective: To investigate the etiology composition and clinical characteristics of bilateral optic disc swelling(ODS). Methods: The medical records of all newly diagnosed bilateral ODS patients admitted to the neurology ward of Beijing Tongren Hospital from January 2017 to June 2021 were retrospectively searched to classify the etiology, obtain demographic and clinical information, and compare the differences in clinical characteristics. Results: A total of 131 patients with bilateral ODS were included, including 56 males and 75 females, aged 15-73 (39±14) years. The most common cause of the bilateral ODS was increased intracranial pressure (ICP)(56/131, 42.7%), followed by optic neuritis (ON)(40/131, 30.5%). Other causes included vascular optic neuropathy (13/131, 9.9%), pseudopilledema (9/131, 6.9%); uveitis (6/131, 4.6%), toxic optic neuropathy (3/131, 2.3%) and unknown causes (4/131, 3.1%). Idiopathic intracranial hypertension (IIH) (43/56, 76.8%) was the most common etiology for papilledema. In the comparison of the two main causes of intracranial hypertension and the clinical characteristics of ON in ODS, there was no statistically significant difference in the incidence of age, gender, complaints of ocular pain or headache, and hemorrhage of optic disc(P>0.05). Visual acuity abnormalities and low vision were more common in ON group than the increased ICP group[36/40(90%) vs 33/56(58.9%), P=0.001; 35/80(43.8%) vs 22/112(19.6%), P<0.001], while severe papilledema was more common in increased ICP group[38/112(33.9%)vs 9/80(11.3%), P<0.001]. Conclusions: The most common cause for bilateral ODS is increased ICP, but it can also be triggered by a variety of other causes. Optic neuritis(ON) is the most important differentiating disease in the study of Chinese patients.

Risk and characteristics of attacks occurring after vaccination in patients with neuromyelitis optica spectrum disorders: A systematic review and meta-analysis.

BACKGROUND: Vaccination in patients with neuromyelitis optica spectrum disorders (NMOSD) is challenging because there is a concern that vaccines can lead to clinical attacks. However, little is known about the risk and the characteristics of attacks occurring after vaccination. METHODS: We performed a systematic review and meta-analysis using PubMed and Embase databases to estimate a summary frequency of attacks occurring after vaccination and describe the clinical features of theses attacks. We defined attacks occurring after vaccination as typical NMOSD attacks that occurred up to 30 days after vaccine administration.  For the frequency of attacks occurring after vaccination, we selected observational studies that reported the number of attacks and total number of patients that received vaccines; for the clinical description of the attacks, case reports and case series were also included. RESULTS: We included 377 participants from 5 studies to estimate the frequency of NMOSD attacks occurring after vaccination. We found a summary frequency of of 2% (95% CI 1-4%, I2 = 0%). We evaluated 17 studies to identify that 13 different vaccines were associated with NMOSD attacks. A higher-than-expected proportion of males, simultaneous optic neuritis and transverse myelitis attacks, and anti-aquaporin 4 antibody negative cases were identified in vaccine-associated attacks from 24 participants from 17 studies. Nearly two-thirds of attacks occurring after vaccination were an initial event of NMOSD. CONCLUSION: The frequency of NMOSD attacks occurring after vaccination is low and non-specific to different vaccine technologies. Our work reinforces the safety of vaccine recommendations in patients with NMOSD.

Optic Neuritis as a Consequence of Long-Term Medical Treatment Using Anastrozole: A Case Report.

BACKGROUND Vision loss secondary to optic neuritis is an uncommon adverse effect of nonsteroidal aromatase inhibitors. There have been few reports in the literature on visual disturbance in patients on long-term treatment with Anastrozole for breast cancer prevention; but none had symptoms worse than blurry vision and/or xerostomia. The present patient had acute onset of right-sided vision loss without other neurologic deficits while using the aromatase inhibitor Anastrozole for breast cancer treatment. CASE REPORT A 69-year-old woman presented to the Emergency Department with approximately 1 month of worsening right eye vision loss that was not associated with any other neurologic deficits or any acute symptoms. The symptom was constant and without alleviating or aggravating factors. After extensive workup with ophthalmologic evaluation, Infectious Disease evaluation, autoimmune tests, brain imaging, lumbar puncture with CSF analysis, and temporal artery biopsy reporting unremarkable results, it was determined that the patient was in an inflammatory state induced by long-term use of Anastrozole, an aromatase inhibitor. CONCLUSIONS The patient's long-term use of Anastrozole likely played a large part in developing right visual disturbance secondary to optic neuritis, as a patient of this age has little risk of developing conditions such as optic neuritis, unilateral loss of vision, and/or autoimmune conditions.

Optic neuritis in lung adenocarcinoma: A challenging diagnosis.

Optic neuritis with CRMP-5 IgG is a paraneoplastic inflammation of the optic nerve associated with lung cancer, mostly small-cell lung cancer. We present the case of a patient with lung adenocarcinoma who developed progressive bilateral visual loss a few months after immune-chemotherapy with pembrolizumab and after Covid-19 vaccination. Positive CRMP-5 IgG were detected in blood sample and complete work-up - including brain MRI - did not show any progression. High dose systemic corticoids were administered with transient improving, followed by intravenous immunoglobulins, methotrexate and rituximab but despite negativization of CRMP-5 IgG, the patient had a progressive visual loss.

Approach to the diagnosis and management of nutritional optic neuropathies.

PURPOSE OF REVIEW: Nutritional deficiency is an under-recognized cause of optic neuropathy. The purpose of this review is to discuss how to identify, diagnose, and appropriately manage patients with nutritional optic neuropathy. RECENT FINDINGS: Nutritional deficiencies have long been thought to be more prevalent in the developing countries. However, with the advent of bariatric surgery, restrictive/selective diets, and the increase in alcohol dependence, it is not uncommon to see nutritional optic neuropathies in the developed world. SUMMARY: Although nutritional optic neuropathy can cause severe and debilitating vision loss, it is often reversible when it is diagnosed and treated in a timely manner.

Sarcoidosis presenting as bilateral optic neuritis after ChAdOx1 nCoV-19 vaccination.

Sarcoidosis is an idiopathic granulomatous disease and can virtually affect any organ system. Multiple factors, including tubercular antigens organic and environmental exposures, have been implicated in its pathogenesis. In addition to drugs, sarcoid-like reactions have been reported following varicella and influenza vaccination. Few reports of erythema nodosum and Lofgren syndrome have been reported after the COVID19 vaccination, though no histologic diagnosis was pursued in these cases. We herein report a case of sarcoidosis presenting with bilateral acute onset vision loss with a temporal association with COVID19 vaccination (ChadOx-1 n-COV, COVISHIELDTM). Symptoms started within two weeks of receiving the vaccine. Alternate causes for optic neuritis were excluded. Transbronchial lung biopsy showed the presence of non-caseating epithelioid cell granulomas. The patient received high-dose corticosteroids immediately after diagnosis, albeit with incomplete clinical improvement in vision on a three-month follow-up. In conclusion, we report a novel case of sarcoidosis-related optic neuritis following COVID19 vaccination.

Optic Perineuritis Presenting as the Initial Manifestation of Central Nervous System Involvement in Rai Stage 0 Chronic Lymphocytic Leukemia.

BACKGROUND: To describe the first case of optic perineuritis because of meningeal involvement of early stage chronic lymphocytic leukemia (CLL). METHODS: A case report and review of the literature. RESULTS: A case of unilateral optic neuropathy associated with enhancement of the optic nerve sheath is described in a patient with a prior 2-year history of Rai Stage 0 CLL. Lumbar puncture revealed a lymphocytic pleocytosis. Cerebrospinal fluid flow cytometry revealed a monoclonal expansion of CD5+ B cells compatible with CLL, matching the flow cytometry characteristics of his peripheral blood. CONCLUSIONS: Optic perineuritis is often initially diagnosed as optic neuritis, yet the 2 have different etiologies and follow a different clinical course. Orbital MRI with contrast structurally separates the 2, revealing a characteristic pattern of peripheral optic nerve sheath rather than primary optic nerve enhancement. Etiologies of optic perineuritis are varied and include inflammatory, infectious, neoplastic, and toxic entities. Central nervous system (CNS) involvement by chronic lymphocytic leukemia is unusual, but cranial nerve and meningeal involvement have been reported. This case adds central nervous system chronic lymphocytic leukemia to the list of differential diagnostic possibilities for optic perineuritis. It also alerts clinicians to consider optic perineuritis as a potential presenting feature of CNS involvement in otherwise asymptomatic and stable CLL.

No Light Perception Vision in Neuro-Ophthalmology Practice.

BACKGROUND: To determine differential diagnosis and visual outcomes of patients with no light perception (NLP) vision related to neuro-ophthalmic conditions. METHODS: Retrospective case series of patients seen at tertiary neuro-ophthalmology practices. Patients were included if they had NLP vision any time during their clinical course. Outcome measures were final diagnosis, treatment, and visual outcome. RESULTS: Seventy-two eyes of 65 patients were included. The average age was 57.6 (range 18-93) years, and 58% were women. The Most common diagnosis (21 patients) was compressive optic neuropathy (CON) with meningioma being the most common culprit (12). Other diagnoses included optic neuritis (ON) (11 patients), infiltrative optic neuropathies (8), posterior ischemic optic neuropathy (7), nonarteritic anterior ischemic optic neuropathy (4), arteritic anterior ischemic optic neuropathy (3), ophthalmic artery occlusion (3), nonorganic vision loss (3), radiation-induced optic neuropathy (2), cortical vision loss (1), retinitis pigmentosa with optic disc drusen (1), and infectious optic neuropathy (1). Ten patients recovered vision: 7 ON, 2 infiltrative optic neuropathy, and 1 CON. Corticosteroids accelerated vision recovery in 7 of the 11 patients with ON to mean 20/60 (0.48 logMAR) over 9.0 ± 8.6 follow-up months. Eleven patients deteriorated to NLP after presenting with at least LP; their diagnoses included CON (3), ophthalmic artery occlusion (2), infiltration (2), ON (1), posterior ischemic optic neuropathy (1), arteritic anterior ischemic optic neuropathy (1), and radiation-induced optic neuropathy (1). CONCLUSIONS: NLP vision may occur because of various diagnoses. Vision recovery was mainly seen in patients with ON. Serious systemic conditions may present or relapse with NLP vision, which clinicians should consider as an alarming sign in patients with known malignancies.

Emerging concepts in the treatment of optic neuritis: mesenchymal stem cell-derived extracellular vesicles.

BACKGROUND: Optic neuritis (ON) is frequently encountered in multiple sclerosis, neuromyelitis optica spectrum disorder, anti-myelin oligodendrocyte glycoprotein associated disease, and other systemic autoimmune disorders. The hallmarks are an abnormal optic nerve and inflammatory demyelination; episodes of optic neuritis tend to be recurrent, and particularly for neuromyelitis optica spectrum disorder, may result in permanent vision loss. MAIN BODY: Mesenchymal stem cell (MSC) therapy is a promising approach that results in remyelination, neuroprotection of axons, and has demonstrated success in clinical studies in other neuro-degenerative diseases and in animal models of ON. However, cell transplantation has significant disadvantages and complications. Cell-free approaches utilizing extracellular vesicles (EVs) produced by MSCs exhibit anti-inflammatory and neuroprotective effects in multiple animal models of neuro-degenerative diseases and in rodent models of multiple sclerosis (MS). EVs have potential to be an effective cell-free therapy in optic neuritis because of their anti-inflammatory and remyelination stimulating properties, ability to cross the blood brain barrier, and ability to be safely administered without immunosuppression. CONCLUSION: We review the potential application of MSC EVs as an emerging treatment strategy for optic neuritis by reviewing studies in multiple sclerosis and related disorders, and in neurodegeneration, and discuss the challenges and potential rewards of clinical translation of EVs including cell targeting, carrying of therapeutic microRNAs, and prolonging delivery for treatment of optic neuritis.

Optic neuritis in Asian type opticospinal multiple sclerosis (OSMS-ON) in a non-Asian population: A functional-structural paradox.

BACKGROUND: Biomarkers have improved the classification of autoimmune inflammatory disorders, including optic neuritis (ON) as a frequent presentation of multiple sclerosis, neuromyelitis spectrum disorders, MOG antibody-related disease (MOGAD), and opticospinal multiple sclerosis (OSMS). The phenotype of OSMS in non-Asian populations is less well known. OBJECTIVE: We investigated the clinical features and prognosis of OSMS-ON in a Brazilian cohort. METHODS: This was a single-center cohort study of patients from Rio de Janeiro (Brazil) with OSMS. All individuals were MOG- and AQP4-seronegative, clinically diagnosed with ON, and had magnetic resonance imaging-confirmed transverse myelitis (TM). Subjects and healthy controls (HCs) were assessed for visual acuity (logMAR VA), automated perimetry mean deviation (MD), intraocular pressure, and spectral-domain optical coherence tomography (OCT), followed by automated retinal layer segmentation of the peripapillary retinal nerve fiber layer (pRNFL) and macular ganglion cell and inner plexiform layer (mGCIPL). Receiver operator characteristic curves were plotted and the area under the curve (AUC) was calculated for group comparisons of retinal asymmetry of the pRNFL and mGCIPL. RESULTS: The 30 patients with OSMS were predominantly female and white. The mean age was 48 years (range 20-70 years). Unilateral ON was the index event in 83.3% of patients. Over the average 18-year follow-up period, there were 89 relapses of ON. In individuals with OSMS, the average VA was 0.07±0.14 in the right eye (RE) and 0.13±0.30 in the left eye (LE). The MD was -5.37±5.88 dB and -5.23±3.34 dB for the RE and LE, respectively. There was a significant cumulative loss of VA (p = 0.0003) and MD (p = 0.0001) with a higher number of recurrent episodes. Atrophy of the pRNFL thickness was significant in OSMS (RE, 78.62 ± 16.01 µm; LE, 79.86 ± 13.79 µm) relative to the HC group (RE, 98.87 ± 10.68 µm; LE, 97.87 ± 10.85 µm, p = 0.0001). Likewise, there was significant mGCIPL atrophy in patients with OSMS (RE, 74.96 ± 14.46 µm; LE, 73.88 ± 13.79 µm) relative to the HC group (RE, 90.50 ± 6.74 µm; LE, 90.41± 6.89 µm; p = 0.0001). Retinal asymmetry, inter-eye percentage, and absolute differences accurately separated patients with unilateral ON from HCs (AUC=0.89 and AUC=0.85, respectively). CONCLUSION: A structural-functional paradox was found in OSMS with a high diagnostic value for a novel metric based on retinal asymmetry. The functional visual outcome are excellent despite significant structural damage to the inner retinal layers in patients with a high ON relapse rate and long-term bilateral sequential involvement.

Clinical significance of Epstein-Barr virus in the cerebrospinal fluid of immunocompetent patients.

INTRODUCTION: Polymerase chain reaction (PCR)-based testing of cerebrospinal fluid (CSF) samples has greatly facilitated the diagnosis of central nervous system (CNS) infections. However, the clinical significance of Epstein-Barr virus (EBV) DNA in CSF of individuals with suspected CNS infection remains unclear. We wanted to gain a better understanding of EBV as an infectious agent in immunocompetent patients with CNS disorders. METHODS: We identified cases of EBV-associated CNS infections and reviewed their clinical and laboratory characteristics. The study population was drawn from patients with EBV PCR positivity in CSF who visited Pusan National University Hospital between 2010 and 2019. RESULTS: Of the 780 CSF samples examined during the 10-year study period, 42 (5.4 %) were positive for EBV DNA; 9 of the patients (21.4 %) were diagnosed with non-CNS infectious diseases, such as optic neuritis, Guillain-Barré syndrome, and idiopathic intracranial hypotension, and the other 33 cases were classified as CNS infections (22 as encephalitis and 11 as meningitis). Intensive care unit admission (13/33 patients, 39.3 %) and presence of severe neurological sequelae at discharge (8/33 patients, 24.2 %) were relatively frequent. In 10 patients (30.3 %), the following pathogens were detected in CSF in addition to EBV: varicella-zoster virus (n = 3), cytomegalovirus (n = 2), herpes simplex virus 1 (n = 1), herpes simplex virus 2 (n = 1), Streptococcus pneumomiae (n = 2), and Enterococcus faecalis (n = 1). The EBV-only group (n = 23) and the co-infection group (n = 10) did not differ in age, gender, laboratory data, results of brain imaging studies, clinical manifestations, or prognosis; however, the co-infected patients had higher CSF protein levels. CONCLUSION: EBV DNA in CSF is occasionally found in the immunocompetent population; the virus was commonly associated with encephalitis and poor prognosis, and frequently found together with other microbes in CSF.

Neuroprotection mediated by ST266 requires full complement of proteins secreted by amnion-derived multipotent progenitor cells.

ST266 is the biological secretome of cultured Amnion-derived Multipotent Progenitor cells containing multiple growth factors and cytokines. While intranasally-administered ST266 improves the phenotype in experimental optic neuritis, specific ST266 components mediating these effects are not known. We compared the effects of ST266 with and without removal of large molecular weight proteins both in vitro and in the multiple sclerosis model experimental autoimmune encephalomyelitis (EAE) in C57BL/6J mice. Mice were treated daily with intranasal vehicle, ST266 or lower molecular weight fraction of ST266. Retinal ganglion cells were counted in isolated retinas, and optic nerves were assessed for inflammation and demyelination. ST266 treatment significantly improved retinal ganglion cell survival and reduced optic nerve demyelination in EAE mice. The lower molecular weight ST266 fraction significantly improved optic nerve demyelination, but only showed a trend towards improved retinal ganglion cell survival. ST266 fractions below 50kDa increased Schwann cell proliferation in vitro, but were less effective than non-fractionated ST266. Demyelination attenuation was partially associated with the lower molecular weight ST266 fraction, but removal of higher molecular weight biomolecules from ST266 diminishes its neuroprotective effects, suggesting at least some high molecular weight proteins play a role in ST266-mediated neuroprotection.

Predictors of Visual Acuity and Usefulness of a Treatment Algorithm in Rhinogenous Optic Neuritis.

Rhinogenous optic neuritis, which causes neuropathy associated with visual dysfunction, greatly reduces patient quality of life and requires suitable early treatment. This study aimed to analyze visual outcome predictors in patients with rhinogenous optic neuritis and to develop and investigate the usefulness of an algorithm to facilitate early treatment. Prospective and retrospective investigations were conducted at the Department of Otorhinolaryngology. The visual outcomes after sinus surgery of 24 of 53 patients suspected of having rhinogenous optic neuritis were analyzed. Furthermore, the usefulness of the treatment algorithm was evaluated in 27 of these 53 patients. Data from 24 patients who underwent surgery were included in a multiple regression analysis to investigate the associations between visual outcomes and concomitant symptoms and the time from symptom onset to surgery. The mean time from the initial examination to a request for otorhinolaryngological examination to assess the usefulness of the treatment algorithm was compared in 27 patients who did not undergo an initial otorhinolaryngological examination. Visual acuity improved in 23 participants who underwent surgery. Multivariate analysis identified the time from onset to surgery and headache as significant predictors of postoperative visual acuity. The mean time from the initial examination to a request for otorhinolaryngological examination was significantly shorter after the algorithm was introduced (1.13 days, 8 patients; P = .008). Early surgical treatment is essential to avoid further postoperative visual acuity decreases in patients with rhinogenous optic neuritis. Patients who experience headache may have poorer postoperative outcomes.

Para-neoplastic optic neuritis presenting in a child with fusion positive localised para-testicular alveolar rhabdomyosarcoma.

We present the case of a 13 year old boy, with sudden onset painful unilateral visual loss, prior to commencing chemotherapy for alveolar rhabdomyosarcoma. Cases of para-neoplastic optic neuritis have been reported in adult cancer patients, however there are no published reports of this phenomenon occurring in children. Our patient had full recovery of his vision, following 6 weeks treatment with steroids, immunoglobulins and standard chemotherapy as per high risk arm of European pediatric soft tissue sarcoma group (EpSSG) Rhabdomyosarcoma (RMS) 2005 guidelines. Our case highlights that para-neoplastic optic neuritis can occur in children. In pediatric patients presenting with optic neuritis and normal auto-antibody screen, an occult or underlying tumor should be considered.

Association of VEGFA, TIMP-3, and IL-6 gene polymorphisms with predisposition to optic neuritis and optic neuritis with multiple sclerosis.

BACKGROUND: The etiology of the inflammatory ON is multifactorial. Much attention is paid to the inflammatory and immune processes that are likely to contribute to the demyelination and MS development. IL-6, VEGFA, and TIMP-3 genes are thought to be involved in the inflammatory processes and manifestation of CNS demyelination, so we aimed to determine the relationship between VEGFA rs1413711, TIMP-3 rs9621532, IL-6 rs1800796 gene polymorphisms and ON, and ON with MS. MATERIALS AND METHODS: Patients with ON, ON with MS, and a random sample of healthy population were enrolled. The genotyping of VEGFA rs1413711, TIMP-3 rs9621532, and IL-6 rs1800796 polymorphisms was carried out using the real-time polymerase chain reaction method. RESULTS: T/C and C/C genotypes of VEGFA rs1413711 were associated with about threefold increased odds of developing ON in the dominant and codominant models. Each allele C at VEGFA rs1413711 was associated with 1.7-fold increased odds of ON development. IL-6 rs1800796 allele C was more frequent in the ON with MS group compared to the control: 17.6% vs. 7.5%, respectively (p = .040). No statistically significant associations were found between TIMP-3 rs9621532 and the ON development. CONCLUSION: VEGFA: rs1413711 is associated with the ON development.

Overlapping central and peripheral nervous system syndromes in MOG antibody-associated disorders.

OBJECTIVE: Antibodies to myelin oligodendrocyte glycoprotein (MOG) are associated with CNS demyelination inclusive of optic neuritis (ON) and transverse myelitis (TM). To examine whether peripheral nervous system (PNS) involvement is associated with MOG antibody-associated disorders (MOGAD), we performed detailed characterization of an Australasian MOGAD cohort. METHODS: Using a live cell-based assay, we diagnosed 271 adults with MOGAD (2013-2018) and performed detailed clinical and immunologic characterization on those with likely PNS involvement. RESULTS: We identified 19 adults with MOGAD and PNS involvement without prior TM. All patients had CNS involvement including ON (bilateral [n = 3], unilateral [n = 3], and recurrent [n = 7]), a cortical lesion (n = 1), meningoencephalitis (n = 1), and subsequent TM (n = 4). Clinical phenotyping and neurophysiology were consistent with acute inflammatory demyelinating polyneuropathy (n = 1), myeloradiculitis (n = 3), multifocal motor neuropathy (n = 1), brachial neuritis (n = 2), migrant sensory neuritis (n = 3), and paresthesia and/or radicular limb pain (n = 10). Onset MRI spine was consistent with myeloradiculitis with nerve root enhancement in 3/19 and normal in 16/19. Immunotherapy resulted in partial/complete PNS symptom resolution in 12/15 (80%) (steroids and/or IV immunoglobulin n = 9, rituximab n = 2, and plasmapheresis n = 1). We identified serum antibodies targeting neurofascin 155, contactin-associated protein 2, or GM1 in 4/16 patients with MOGAD PNS compared with 0/30 controls (p = 0.01). There was no binding to novel cell surface antigens using an in vitro myelinating sensory neuronal coculture model. CONCLUSIONS: Myeloradiculitis, combined central and peripheral demyelination syndromes, and inflammatory neuropathies may be associated with MOGAD and may be immunotherapy responsive. We identified a subgroup who may have pathology mediated by coexistent autoantibodies.

Infliximab-induced optic neuritis.

Antitumour necrosis factor alpha agents are important treatments in many inflammatory conditions including rheumatoid arthritis, psoriatic arthritis and the inflammatory bowel diseases. However, there have been case reports of optic neuritis and other demyelinating diseases as complications of these agents. This case report presents a patient with ulcerative colitis on infliximab who presented with sudden onset mono-ocular visual field loss and highlights the diagnosis and management of infliximab-induced optic neuritis.