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Background: Multiple sclerosis (MS) is a chronic inflammatory demyelinating autoimmune disease of the central nervous system (CNS) with axonal degeneration as major determinant of neurological disability. Assessment of unmyelinated retinal nerve fibers using optical coherence tomography (OCT) may be useful for diagnosing the onset and rate of progression of neurodegeneration., Objective: To assess the incidence and severity of damage of the peripapillary retinal nerve fiber layer (RNFL) in two different MS subtypes: non-progressive [Prog(-)MS] and progressive [Prog(+)MS]., Methods: 48 patients (96 eyes) with MS were included: 13 males, 35 females; aged 22-62 years (mean 38.8; SD ± 10.02) in two subgroups: 26 Prog(-)MS and 22 Prog(+)MS. 3 subtypes of Prog(+)MS were identified by neurologist, according to Lublin criteria: 3 patients had PPMS (14%), 7 had SPMS(32%), 12 had PRMS(54%). RRMS subtype was considered a non-progressive phenotype, designated as Prog(-)MS. All 22 patients with progressive MS phenotypes were included in one group, designated as Prog(+)MS. Progressive disease can be defined over 1 year. The expanded EDSS score was determined by the treating MS specialist and confirmed by the study investigators through the records review. Definition included a 3-strata progression magnitude in the absence of a relapse, confirmed after 3 months within the leading Functional System and required an Expanded Disability Status Scale step≥4 and pyramidal score≥2. 11 Prog(-)MS (16 eyes) and 10 Prog(+)MS (13 eyes) patients had a history of optic neuritis (ON). EDSS score was 1.5-6.5 (mean 3.83 ± 1.62) in the Prog(+)MS group and 1.0-3.5 (mean 1.40 ± 0.57) in the Prog(-)MS., Control Group: 31 healthy volunteers (3 males, 28 females), aged 20-62 years (mean 37.4 ± 10.88). Peripapillary RNFL thickness was measured around the optic nerve head (ONH) using spectral-domain OCT (Topcon OCT 1000 MarkII, FastMap v. 3.40, Topcon, Japan). Scans were obtained according to OSCAR-IB consensus criteria. The generalized estimating equation model (GEE) was used in the statistical analysis to assess differences in RNFL thickness between Prog(-)MS and Prog(+)MS patients, taking into consideration history of ON, EDSS score, immunomodulatory therapy, MS progression, MS duration, age and gender. The protocol was approved by the Ethical Committee of the Medical Centre of Postgraduate Education, Warsaw, Poland and informed consent was obtained from all subjects., Results: There was a significant difference between Prog(-)MS and Prog(+)MS groups for mean, nasal and superior quadrant of RNFL thickness. For individuals with a history of ON, significant differences were found between the two MS phenotypes regardless of RNFL thickness measurements., Conclusions: A significant correlation was established between RNFL thickness and progression of neurodegeneration in MS patients with no regard to history of ON. RNFL thickness may be considered a MS biomarker and potential diagnostic tool for assessment of disease progression., (Copyright © 2018. Published by Elsevier B.V.)

Optic neuritis (ON) is an inflammatory condition that causes demyelination and thickening of the optic nerve leading to acute/subacute vision loss. It is frequently associated with other conditions like multiple sclerosis, but is often misdiagnosed, which can lead to a suboptimal prognosis. Ultrasound is rarely utilized to help make this diagnosis, even though it can easily detect a thickened retrobulbar optic nerve sheath diameter. We describe four cases in which ultrasonographic measurement of the optic nerve sheath diameter aided in the diagnosis of ON., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background and Purpose: Optic neuritis (ON) is a common clinical manifestation of Multiple Sclerosis (MS), which is associated with reduced visual acuity, blurred vision, blindness and retro-bulbar pain. In several studies, specific relations between optic nerve diameter and hemodynamics of the eye bulb arteries with ON have been reported. However, no consensus has been reached in this regard. We aim at determining the alterations in optic nerve diameter and eye bulb arteries hemodynamics in ON in MS patients., Methods: This case-control study includes 40 patients, who at least had experienced one phase of ON, in one of their eyes. To measure hemodynamics of arteries in the affected eyes, a color Doppler imaging was performed and end diastolic velocity (EDV), peak systolic velocity (PSV), peripheral resistance indices i.e. resistance index (RI) and pulsatile index (PI) were measured in posterior ciliary artery (PCA) and ophthalmic artery (OA). Also, optic nerve diameter was measured using sonography. Non-affected eyes of these patients were considered as control group., Results: There were no significant differences in EDV, PSV, RI and PI in PCA and OA. The mean optic nerve diameter in the affected eyes was 4.73 mm, whereas, it was 4.31 mm in unaffected eyes, which was significantly different (P = .02)., Conclusion: These results indicate that there is a significant relation between eye involvement and increased optic nerve diameter in MS patients with chronic ON. While, there were no significant relations in EDV, PSV, RI and PI in PCA and OA comparing two groups., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: Limited prospective information exists regarding spectral-domain optical coherence tomography (SD-OCT) in secondary progressive multiple sclerosis (SPMS)., Objective: Document cross-sectional and longitudinal retinal nerve fiber layer (RNFL) and macular ganglion cell plus inner plexiform layer (GCIPL) features of an SPMS clinical trial cohort., Methods: Prospective, observational study using a 2-year randomized placebo-controlled SPMS trial cohort with yearly SD-OCT testing. Post hoc analysis determined influences of optic neuritis (ON), disease duration, and baseline SD-OCT on annualized atrophy rates and on correlations between OCT and brain atrophy., Results: Mean RNFL and GCIPL values of patients ( n = 47, mean age = 59 years, mean disease duration = 30 years) were significantly lower among eyes with prior ON than those without (no history of ON (NON)). Annualized RNFL (-0.31 µm/year) and GCIPL (-0.29 µm/year) atrophy rates did not differ between ON and NON eyes. Baseline RNFL thickness >75 µm was associated with greater annualized RNFL atrophy (-0.85 µm/year). Neither RNFL nor GCIPL atrophy correlated with whole-brain atrophy., Conclusion: This study suggests that eyes with and without ON history may be pooled for atrophy analysis in SPMS clinical trials using SD-OCT. Low baseline RNFL, small retinal atrophy rates, and lack of correlation with whole-brain atrophy in this population are important trial design considerations.

Background: Limbic encephalitis is characterized by rapid onset of working memory deficit, mood changes, and often seizures. The condition has a strong paraneoplastic association, but not all cases are invariably due to tumors., Case Presentation: We present a case of limbic encephalitis in a Chinese patient who initially presented to our hospital with optic neuritis and no other neurological symptoms. The diagnosis was made radiologically, and cognitive and neurological symptoms did not occur until 5 months later. Extensive investigations for autoimmune, infective, and neoplastic causes were all negative. A working diagnosis of paraneoplastic neurological syndrome was made, and the patient is being managed with high-dose steroid therapy according to the Optic Neuritis Treatment Trial protocol during relapses, as well as with tumor surveillance., Conclusions: This case highlights ocular symptoms as important clues for diagnosing neurological diseases, as well as autoimmune encephalitis as an important differential diagnosis in the management of "idiopathic" optic neuritis in the Chinese population.

Objectives: To measure early structural damage caused by autoimmune inflammatory optic neuritis (ON) by optical coherence tomography (OCT) in a population-based cohort., Methods: In a prospective population-based study over 24 months in Southern Denmark, patients diagnosed with acute ON and without prior diagnosis of a chronic neuroinflammatory disorder were included and examined with OCT, visual evoked potentials (VEP), visual fields, high contrast visual acuity (HCVA), and low contrast letter acuity (LCLA). Structural and functional outcomes were determined at 6-month follow-up based on interocular differences., Results: The 50 included patients had on average 16.9 μm peripapillary retinal nerve fiber layer loss, 10.6 μm ganglion cell and inner plexiform layer (GCIP) loss, and an average HCVA decrease of 0.22 dec. Based on a linear regression model, average GCIP loss amounted to -0.2 μm per day and started 8 days after onset. OCT outcomes but not VEP correlated well with all visual function measurements at follow-up. Structural and functional damage in 20 patients (40%) diagnosed de novo with multiple sclerosis (MS) and in 2 patients (4%) with positive myelin oligodendrocyte glycoprotein antibodies (MOG-IgG) test did not differ from patients with idiopathic ON., Conclusions: Optic neuritis causes substantial retinal damage and vision loss independent of the underlying disease. Our study supports that GCIP damage starts closely to clinical onset. Good structure-function correlations between OCT and vision support the importance of OCT in monitoring acute ON., (© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Diphtheria, tetanus, pertussis, and inactivated poliovirus combined vaccine is widely used in young children as part of a series of immunizations before they start attending school. Case studies of demyelinating conditions following administration of diphtheria, tetanus, pertussis, and polio vaccine have been reported, but none so far resulting in optic neuritis. This report further contributes to the database of central nervous system demyelinating conditions affiliated with receipt of vaccines., Case Presentation: A previously healthy 27-year-old Hispanic man presented to an emergency department with headache, periorbital pressure, pain with ocular movements, and intermittent blurred vision that developed 1 day after administration of the diphtheria, tetanus, pertussis, and inactivated poliovirus combined vaccine. A diagnosis of optic neuritis was made via ophthalmic examination with fundus photography and automated Humphrey visual field analysis. His vision recovered following treatment with high-dose intravenously administered methylprednisolone followed by a tapered dose of orally administered prednisolone., Conclusions: Although the association between immunizations and the onset of central nervous system demyelinating conditions is well documented, this report, to the best of our knowledge, is the first case of optic neuritis following diphtheria, tetanus, pertussis, and inactivated poliovirus combined vaccination. Inclusion of this case report in the medical community will allow for broader understanding of possible conditions that may present shortly after receipt of vaccination.

Papilloedema and raised intracranial pressure have been frequently reported with hypoparathyroidism, but very rarely optic neuritis. We report a case of a 54-year-old male patient who presented with classical optic neuritis which is believed to be secondary to primary hypoparathyroidism., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2018. No commercial re-use. See rights and permissions. Published by BMJ.)

Background and Purpose: Few recent data are available concerning idiopathic optic neuritis (ON). We aimed to describe a large cohort of patients with idiopathic ON. We compared this cohort with patients with ON related to myelin oligodendrocyte glycoprotein (MOG) or ON related to aquaporin-4 (AQP4) antibodies., Methods: This was a monocentric retrospective observational study. Inclusion criteria for idiopathic ON were as follows: age ≥ 16 years, follow-up of at least 2 years, negative for antibodies against MOG and AQP4 immunoglobulin G, and no magnetic resonance imaging (MRI) lesions suggestive of demyelination (two brain MRI scans, one at baseline and one during follow-up, and one spinal cord MRI scan)., Results: Among 23 patients with idiopathic ON (female, 82.6%; median age, 36 years; median follow-up time, 41.4 months), 56.5% had recurrent ON (median time to a second ON episode, 6 months). The final visual acuity in this group (median, 0; mean, 0.43; range, 0-3) was similar to that in the AQP4 group (n = 18; P-value after Bonferroni correction = 0.936) but worse than that in the MOG group (n = 25; P-value after Bonferroni correction = 0.019). At the last evaluation, visual acuity levels were ≤0.5 and <0.2, respectively, in 36.8% and 21% of the idiopathic ON group, 58.3% and 26.7% of the AQP4 group, and 0% and 0% of the MOG group., Conclusion: The recovery of visual acuity among patients with idiopathic ON was poor, similar to that observed in the AQP4 group., (© 2018 EAN.)

This overview is especially intended for practitioners in ophthalmology. It focuses on how to handle diseases affecting the optic pathway with MRI in general and in particular. Several tables accompany this article, in order to illustrate the different MRI scanning protocols, properties of frequently used MRI sequences, as well as common pathologies to be found in the optic pathway. With the help of exemplary cases, the application and interpretation of MRI imaging will be shown. There is a tremendous variety of diseases influencing the optic pathway - which is why this article does not intend to give a complete representation of this medical issue, but rather focuses on giving hands-on guidance (through multiple tables) for daily routine. Moreover, the article also addresses the issue of retained gadolinium in the brain., Competing Interests: Die Autoren geben an, dass kein Interessenkonflikt besteht., (Georg Thieme Verlag KG Stuttgart · New York.)

Background: Anti-myelin oligodendrocyte glycoprotein (MOG) antibody (Ab) can be found in different immune-mediated inflammatory CNS disorders. The full range of clinical manifestations may not have been fully discovered yet., Methods: In a cross-sectional study 184 adults (age ≥ 16) were tested for anti-MOG antibody (Ab) with a cell-based assay. To define the relevant target population for anti-MOG antibody testing in a neurology clinic, we divided the entire study population based on the presenting symptoms and classified cases followed for multiple sclerosis (MS) according to the clinical features and response to disease-modifying therapy., Results: We identified eight (4.4%) MOG-Ab positive cases in the whole cohort. All eight cases had first manifestations suggestive of neuromyelitis optica spectrum disorder (NMOSD), but had highly variable disease courses and responses to therapy. This included a patient with chronic relapsing inflammatory optic neuropathy (CRION) responding only to therapy with infliximab. Four (3%) out of 134 cases followed for MS who tested positive for anti-MOG Ab showed atypical features and had poor response to therapy., Conclusion: A broad range of clinical and radiological features of anti-MOG associated disorder was observed in a single centre. MOG-Ab testing should be considered in patients with an NMOSD phenotype and in MS patients presenting atypical features. The potential use of infliximab therapy for MOG-Ab disease should be further investigated., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Purpose: To characterize the clinical phenotype of myelin oligodendrocyte glycoprotein antibody (MOG-IgG) optic neuritis., Design: Observational case series., Methods: Setting: Multicenter. Patient/Study Population: Subjects meeting inclusion criteria: (1) history of optic neuritis; (2) seropositivity (MOG-IgG binding index > 2.5); 87 MOG-IgG-seropositive patients with optic neuritis were included (Mayo Clinic, 76; other medical centers, 11). MOG-IgG was detected using full-length MOG-transfected live HEK293 cells in a clinically validated flow cytometry assay., Main Outcome Measures: Clinical and radiologic characteristics and visual outcomes., Results: Fifty-seven percent were female and median age at onset was 31 (range 2-79) years. Median number of optic neuritis attacks was 3 (range 1-8), median follow-up 2.9 years (range 0.5-24 years), and annualized relapse rate 0.8. Average visual acuity (VA) at nadir of worst attack was count fingers. Average final VA was 20/30; for 5 patients (6%) it was ≤20/200 in either eye. Optic disc edema and pain each occurred in 86% of patients. Magnetic resonance imaging showed perineural enhancement in 50% and longitudinally extensive involvement in 80%. Twenty-six patients (30%) had recurrent optic neuritis without other neurologic symptoms, 10 (12%) had single optic neuritis, 14 (16%) had chronic relapsing inflammatory optic neuropathy, and 36 (41%) had optic neuritis with other neurologic symptoms (most neuromyelitis optica spectrum disorder-like phenotype or acute disseminated encephalomyelitis). Only 1 patient was diagnosed with MS (MOG-IgG-binding index 2.8; normal range ≤ 2.5). Persistent MOG-IgG seropositivity occurred in 61 of 62 (98%). A total of 61% received long-term immunosuppressant therapy., Conclusions: Manifestations of MOG-IgG-positive optic neuritis are diverse. Despite recurrent attacks with severe vision loss, the majority of patients have significant recovery and retain functional vision long-term., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Introduction: Aquaporin-4 antibody (AQP4-Ab) is specific for neuromyelitis optica spectrum disorder (NMOSD) and so is helpful to distinguish NMOSD from other autoimmune diseases. Several viral infections may play a role in the onset of NMOSD., Case Report: We describe a case of a previous healthy 82-year-old woman who presented with acute visual loss occurring 3 weeks after scrub typhus. Physical examination showed a relatively afferent pupillary defect in the right eye and ophthalmoscopy revealed edema of the right optic disc. Enhanced magnetic resonance imaging revealed enhancement of the right optic nerve. Serological testing showed AQP4-Ab. After methylprednisolone pulse therapy followed by oral tapering of prednisolone, visual dysfunction was improved. Subsequently she experienced no attacks for 5 years., Conclusions: Optic neuritis (ON) associated with scrub typhus is extremely rare. Our case support that scrub typhus could trigger ON in a lifelong asymptomatic patient with AQP4-Ab and AQP4-Ab should be considered in a very old age patient with suspected postinfectious inflammatory ON.

Background: Herpes zoster ophthalmicus (HZO) is an inflammation related to reactivation of the latent varicella zoster virus (VZV), involving the ophthalmic branch of the trigeminal nerve. Optic neuritis (ON), a rare ocular complication following HZO, has been reported in 1.9% of HZO-affected eyes. Most previous cases occurred simultaneously with other ocular complications, especially orbital apex syndrome. Moreover, detailed magnetic resonance imaging (MRI) with diffusion weighted imaging of the optic nerve and trigeminal nucleus in HZO-related ON has been rarely reported. We report a case of postherpetic isolated ON with a concurrent abnormal trigeminal nucleus on imaging., Case Presentation: A healthy 58-year-old female presented with sudden painful visual loss in her right eye for 2 days. Four weeks before the presentation, her right eye was diagnosed with HZO, and she received intravenous acyclovir for 10 days. Ophthalmic examination revealed a visual acuity of light perception and 20/20 in the right and left eyes, respectively. A relative afferent pupillary defect was present in the right eye. Neurological examination was significant for hypoesthesia in the area of the HZO. A clinical diagnosis of HZO-related right retrobulbar ON was made, and other causes of atypical ON were excluded. MRI showed enhancement and restricted diffusion of the right-sided optic nerve with linear hyperintense T2 of the right-sided spinal trigeminal nucleus and tract (STNT) along the brainstem. She received 14 days of intravenous acyclovir and 5 days of methylprednisolone. Both were switched to an oral route for 2 months. After the completion of treatment, the visual acuity was counting fingers and 20/20 in the right eye and left eye, respectively. Stable brainstem STNT abnormalities and resolution of ON were found radiologically., Conclusions: Isolated ON is a rare ocular complication following HZO. An abnormal high signal of STNT on a T2 weighted image may be present, which may be a clue for VZV-associated complications, such as HZO-related ON, especially in cases lacking an obvious history of HZO or other concomitant ocular complications. Prompt treatment with both acyclovir and corticosteroids should be started. Restricted diffusion of the optic nerve may be a predictor for poor visual recovery.

We present a method for optic nerve head (ONH) 3-D shape analysis from retinal optical coherence tomography (OCT). The possibility to noninvasively acquire in vivo high-resolution 3-D volumes of the ONH using spectral domain OCT drives the need to develop tools that quantify the shape of this structure and extract information for clinical applications. The presented method automatically generates a 3-D ONH model and then allows the computation of several 3-D parameters describing the ONH. The method starts with a high-resolution OCT volume scan as input. From this scan, the model-defining inner limiting membrane (ILM) as inner surface and the retinal pigment epithelium as outer surface are segmented, and the Bruch's membrane opening (BMO) as the model origin is detected. Based on the generated ONH model by triangulated 3-D surface reconstruction, different parameters (areas, volumes, annular surface ring, minimum distances) of different ONH regions can then be computed. Additionally, the bending energy (roughness) in the BMO region on the ILM surface and 3-D BMO-MRW surface area are computed. We show that our method is reliable and robust across a large variety of ONH topologies (specific to this structure) and present a first clinical application., ((2018) COPYRIGHT Society of Photo-Optical Instrumentation Engineers (SPIE).)

Objective: To evaluate volumetric changes and discriminative power of intra-retinal layers in early-stage multiple sclerosis (MS) using a 3D optical coherence tomography (OCT) imaging method based on an in-house segmentation algorithm., Methods: 3D analysis of intra-retinal layers was performed in 71 patients with early-stage MS (mean disease duration 2.2 ± 3.5 years) at baseline and 40 healthy controls (HCs). All patients underwent a follow-up OCT scan within 23 ± 9 months. Patients with a clinical episode of optic neuritis (ON) more than 6 months prior to study entrance were compared with patients who never experienced clinical symptoms of an ON episode (NON)., Results: Significantly decreased total retinal volume (TRV), macular retinal nerve fiber layer (mRNFL) and ganglion cell-inner plexiform layer (GCIPL) volumes were detected in ON patients compared to NON patients (all p values < 0.05) at baseline. Each parameter on its own allowed identification of prior clinical ON based on a discriminative model (ROC analysis). Over time, TRV decreased in both ON (p = 0.013) and NON patients (p = 0.002), whereas mRNFL volume (p = 0.028) decreased only in ON and GCIPL volume (p = 0.003) decreased only in NON patients., Conclusion: Our 3D-OCT data demonstrated that TRV, mRNFL and GCIPL allow discrimination between ON and NON patients in a cross-sectional analysis. However, the subsequent retinal atrophy pattern diverges in the initial phase of MS: Prior ON promotes sustained axonal thinning over time indicated by mRNFL loss, whereas longitudinal measurement of GCIPL volume better depicts continuous retrograde neurodegeneration in NON patients in early-stage MS.

Objective: To investigate the effect of including optic nerve involvement in dissemination in space (DIS) criteria for diagnosis of multiple sclerosis (MS) in patients with clinically isolated syndrome (CIS)., Methods: We studied 160 patients with CIS: 129 with optic neuritis (ON) and 31 with non-ON CIS. MRI brain/spinal cord was done at the time of presentation and a follow-up MRI brain after 3-12 months. We evaluated optic nerve involvement clinically or with visual evoked potentials (VEPs, n = 42). We investigated the performance of the McDonald 2017 DIS criteria and modified DIS criteria including optic nerve involvement for development of clinically definite MS after ∼15 years., Results: In the ON group, including symptomatic optic nerve involvement identified an additional 15 patients with DIS. The modified DIS criteria that included optic nerve involvement were more sensitive (95% vs 83%) and more accurate (81% vs 78%) than the McDonald 2017 DIS criteria, but less specific (57% vs 68%). In combination with dissemination in time criteria, the modified DIS criteria remained more sensitive (83% vs 74%) and accurate (81% vs 75%), and the specificity was the same (77%). Including asymptomatic optic nerve involvement in DIS the non-ON group did not identify any additional patients and the performance of the McDonald 2017 criteria and the modified criteria was the same., Conclusion: The inclusion of symptomatic optic nerve involvement in DIS in patients with ON improved the overall performance of MS diagnostic criteria. Including asymptomatic optic nerve involvement in DIS in patients with a non-ON CIS may be of limited value., Classification of Evidence: This study provides Class III evidence that for patients with suspected MS, inclusion of symptomatic optic nerve involvement in DIS criteria improves the overall performance of diagnostic criteria for MS., (© 2018 American Academy of Neurology.)

Purpose: Single-shot echo-planar imaging is the conventional diffusion-weighted imaging (C-DWI) sequence for evaluating orbital disease. However, its utility is restricted in small organs like the chiasma and optic nerve. This study was conducted to investigate the utility of field-of-view optimized and constrained undistorted single-shot diffusion-weighted imaging (FOCUS-DWI) for evaluating the chiasma and optic nerve in acute optic neuritis, making comparisons with C-DWI., Methods: FOCUS-DWI and C-DWI were performed on 36 acute optic neuritis patients and 16 normal controls. Two readers assessed image quality using 5-point Likert scales. Differences in the visual assessments and apparent diffusion coefficient (ADC) values between C-DWI and FOCUS-DWI were evaluated. Inter-observer agreement in the qualitative data was assessed using Cohen's kappa coefficients. Inter- and intra-observer agreements in the ADC values were evaluated using intraclass correlation coefficients., Results: FOCUS-DWI was superior to C-DWI in all aspects of the image evaluations. The Cohen's kappa coefficients for FOCUS-DWI were almost perfect (0.81-1) or substantial (0.61-0.80) for all the image quality categories. In the FOCUS-DWI images, the structural conspicuity of the chiasma and canalicular and cisternal segments was significantly superior on coronal views than on axial views (P < 0.0001). ROC analysis showed that in optic neuritis patients, the diagnostic value of ADC measurements on FOCUS-DWI was higher than ADC values measured on C-DWI., Conclusion: The FOCUS-DWI technique can provide substantial improvements over C-DWI for imaging different aspects of the optic nerve and chiasma. The coronal scan direction is more suitable than the axial scan direction for FOCUS-DWI.

Background: The effect of rituximab on acute disseminated encephalomyelitis (ADEM) followed by recurrent optic neuritis (ON) is not yet known., Patient: We are reporting the case of a 4-year-old Japanese girl who was diagnosed with anti-myelin oligodendrocyte glycoprotein (MOG) antibody positive ADEM followed by recurrent ON. She developed altered mental status, left facial paralysis, left paresis, and experienced three episodes of ON. She was treated with rituximab and azathioprine (AZA) as prevention for recurrent ON. She relapsed under treatment with AZA when CD19 cells reappeared 6 months after the first rituximab infusion. However, she has not relapsed since her CD19 count was reduced and kept low with rituximab infusion., Conclusions: It is conceivable that anti-MOG antibodies are involved in the pathology of "ADEM followed by recurrent ON," and that the early introduction of rituximab, which is involved in the suppression of antibody production and has effects on CD20 T lymphocytes, may be a feasible treatment for ON. Due to the small number of patients, additional reports on prospectively followed patients are needed., (Copyright © 2018 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.)

Purpose: In clinical practice, acute optic neuritis (ON) associated with the development of neuromyelitis optica (NMO) after the first attack is often indistinguishable from that associated with multiple sclerosis (MS). We aimed to determine the optimal combination of features derived from conventional magnetic resonance imaging (MRI) and diffusion-weighted imaging using readout-segmented echo-planar imaging (RESOLVE-DWI) for the differentiation of these conditions., Materials and Methods: Orbital conventional MRI and RESOLVE-DWI were performed using a 3.0-T scanner on 54 patients with acute ON (26 NMO-related and 28 MS-related). The features detected by conventional MRI (including laterality, the enhancement pattern, and the extent and position of involvement) and the apparent diffusion coefficient (ADC) measurements were retrospectively compared between the NMO-related and MS-related groups. A multivariate logistic regression analysis was used to identify the most significant variables, and receiver operating characteristic curve analyses were performed to determine the ability of a combined diagnostic model based on the qualitative and quantitative characteristics identified in this study to differentiate the 2 conditions., Results: The multivariate logistic regression analyses indicated that the presence of chiasm involvement and lower ADC values were significantly associated with NMO-related acute ON compared with MS-related acute ON (P = 0.037 and 0.008, respectively). The diagnostic criterion of chiasm involvement or "ADC < 791 × 10 mm/s and chiasm involvement" had the highest specificity (96.9%), and "ADC < 791 × 10 mm/s or chiasm involvement" showed the optimal sensitivity (77.8%) for differentiating NMO-related from MS-related acute ON., Conclusions: Conventional MRI RESOLVE-DWI is helpful for differentiating NMO-related acute ON from MS-related acute ON. The combination of the ADC value chiasm involvement appears to be effective for discriminating these 2 types of acute ON.

The diagnosis of the recurrent optic neuritis is commonly established clinically, and sometimes it could be challenging because the involved optic nerve does not always show significant enhancement on conventional contrast enhanced-T1 weighted imaging (CE-T1WI). In this paper, we reported a middle-aged female with early diagnosis of recurrent optic neuritis using contrast-enhanced T2 fluid-attenuated inversion recovery imaging (CE-T2FLAIR). The involved optic nerve presented evident enhancement on CE-T2FLAIR and no enhancement on CE-T1WI. This case suggested that the CE-T2FLAIR may be a useful diagnostic tool specifically for the recurrent optic neuritis in clinical practice.

Purpose of Review: Clinical trials using agents directed at neuroprotection and remyelination in multiple sclerosis (MS) are needed. As optic neuritis (ON) is common in people with MS and the pathology of ON is similar to other MS lesions in the brain, measurements of the anterior visual system are frequently utilized in neuroprotection and remyelination trials. Understanding the strengths and weaknesses of the measurements is vital when interpreting the results of this research., Recent Findings: Techniques such as visual evoked potentials (VEP) and optical coherence tomography (OCT) are well established in MS and are thought to measure axonal integrity and myelination. Novel imaging techniques can also be used in conjunction with these measurements to provide better insight into optic nerve structure and function. Magnetization transfer imaging (MTR) together with optic nerve area and volume measures neurodegeneration; diffusion tensor imaging (DTI) measures myelination status and neurodegeneration. However, these techniques require various levels of experience to interpret, and all can be confounded by ocular motion and surrounding fat and bone. This article provides a review of established and novel techniques to measure the anterior visual system in multiple sclerosis with a focus on the evidence to support their use as outcome measures in clinical trials focused on neuroprotection and remyelination therapies.

Objective: To evaluate the injury of retinal microstructure using optical coherence tomography (OCT) and investigate the role of aquaporin 4 antibody (AQP4 Ab) in this injury process. Methods: Forty patients with neuromyelitis optica spectrum disorders (NMOSD) were retrospectively studied, each of whom reported at least one episode of optic neuritis (ON), namely 59 ON eyes involved in all. All patients were divided into two subgroups based on AQP4 Ab tests including 25 patients (37 ON eyes) with AQP4 positive (Ab(+)/NMOSD group) and 15 patients (22 ON eyes) negative (Ab(-)/NMOSD group). In addition, 10 healthy controls (20 eyes) matched for age and sex (HC group) were analyzed. Spectral domain optical coherence tomography (SD-OCT) was used to quantify peripapillary retinal nerve fiber layer (RNFL). Nonparametric test was used to compare differences between groups. Results: Age distribution and gender ratio were comparable in three groups ( P> 0.05). Visual acuity in ON eyes of Ab(+)/NMOSD group was worse than that of Ab(-)/NMOSD group ( P= 0.02). There were no significant differences between Ab(+)/NMOSD and Ab(-)/NMOSD in aspects of disease duration (2.6 vs. 1.9 year), ON episodes (2 vs. 1), longitudinal extensive transverse myelitis (LETM) ratio (48.0% vs. 66.7%), NMOSD specific intracranial lesions ratio (32.0% vs. 53.3%), positive autoimmune antibody ratio (52.0% vs. 20.0%) ( P= 0.13, 0.08, 0.25, 0.18, 0.06, respectively). The thickness of temporal, superior, nasal, inferior and average RNFL in ON eyes of both Ab(+)/NMOSD and Ab(-)/NMOSD group were thinner than those in eyes of HC group (all P< 0.05). The thickness of superior and inferior RNFL in ON eyes of Ab(+)/NMOSD were 61.0 μm and 62.0 μm, which was thinner than those of Ab(-)/NMOSD 94.5 μm and 97.0 μm ( P= 0.03 and 0.01, respectively). Conclusions: RNFL reflects the injury of retinal microstructure in NMOSD patients. AQP4 Ab seropositivity is correlated to the severity of RNFL damage, implying the potential role of AQP4 Ab in this pathological process.

Background: The clinical characteristics of patients with pediatric optic neuritis with seropositive myelin oligodendrocyte glycoprotein antibodies in Asia have not been reported., Methods: Patients ≤18 years-old with acute-onset optic neuritis were enrolled. Serum myelin oligodendrocyte glycoprotein and aquaporin-4 antibodies were detected and patients were followed for at least six months. The clinical features were evaluated among myelin oligodendrocyte glycoprotein-seropositive optic neuritis, aquaporin-4-seropositive optic neuritis, and double seronegative optic neuritis. Best-corrected visual acuity, thickness of optic disc retinal nerve fiber layer, and macular ganglion cell complex were measured by optical coherence tomography., Results: Among myelin oligodendrocyte glycoprotein-optic neuritis, aquaporin-4-optic neuritis, and seronegative-optic neuritis, the percentages of best-corrected visual acuity measured better than 0.8 (20/25) at the six-month visit were 89.47%, 33.33%, and 82.26%, respectively, a rate that is significantly better in patients with myelin oligodendrocyte glycoprotein-optic neuritis and seronegative-optic neuritis (P = 0.02). The average peripapillary retinal nerve fiber layers were 58.03 ± 8.73 µm, 64.34 ± 12.88 µm, and 78.12 ± 13.34 µm for the patients with myelin oligodendrocyte glycoprotein-optic neuritis, aquaporin-4-optic neuritis, and seronegative-optic neuritis, respectively, which showed no statistical difference between patients with myelin oligodendrocyte glycoprotein-optic neuritis and aquaporin-4-optic neuritis (P = 0.089), but were both thinner than patients with seronegative-optic neuritis (P = 0.001)., Conclusions: The recovery of visual acuity in patients with myelin oligodendrocyte glycoprotein-optic neuritis was as good as in patients with seronegative-optic neuritis, and the retinal nerve fiber layer of the optic nerve head showed thinning as severe as that of the patients with aquaporin-4-optic neuritis., (Copyright © 2018 Elsevier Inc. All rights reserved.)

To summarize recent findings regarding the utility of optical coherence tomography in multiple sclerosis. We searched PubMed for relevant articles using the keywords 'optical coherence tomography multiple sclerosis'. Additional articles were found via references in these articles. We selected articles based on relevance. Optical coherence tomography has contributed to greater insights into the pathophysiology of multiple sclerosis. Loss of retinal nerve fibre layer and ganglion cell layer thickness correlate with clinical and paraclinical parameters such as visual function, disability and magnetic resonance imaging. Some studies indicate that OCT parameters may be able to predict disability progression and visual function in MS. OCT angiography has recently emerged as a novel technique to study MS. OCT has proven very useful with regards to research, monitoring and predicting disability in multiple sclerosis. It will be interesting to see how OCT angiography will contribute to this field.

Background: To identify the extent of ganglion cell damage after first-time optic neuritis (ON) using the inter-ocular difference between affected and fellow eyes, and whether this approach is able to detect more patients suffering from ganglion cell damage than using absolute values., Methods: Thirty-four patients with first-time unilateral ON were followed for a median 413 days. Patients underwent optical coherence tomography testing to determine ganglion cell plus inner plexiform layer thickness (GCIP). Ganglion cell loss was quantified as GCIP difference between ON-affected and fellow eyes (inter-GCIP) and was compared against measurements from 93 healthy controls (HC). Visual function was assessed with high contrast visual acuity; and standard automated perimetry-derived measures of mean deviation and foveal threshold., Results: At clinical presentation after median 19 days from symptom onset, 47.1% of patients showed early GCIP thinning in the ON-affected eye based on inter-GCIP. At the last visit acute ON was associated with 16.1 ± 10.0 µm GCIP thinning compared to fellow eyes (p = 3.669e-06). Based on inter-GCIP, 84.9% of ON patients sustained GCIP thinning in their affected eye at the last visit, whereas using absolute values only 71.0% of patients suffered from GCIP thinning (p = 0.002076). Only 32.3% of these patients had abnormal visual function. The best predictor of GCIP thinning as a measure of ON severity at the last visit was worse visual field mean deviation at clinical presentation., Conclusion: Inter-ocular GCIP identifies significantly more eyes suffering damage from ON than absolute GCIP, visual fields or visual acuity loss. Effective interventional options are needed to prevent ganglion cell loss., (Copyright © 2018. Published by Elsevier B.V.)

What should physicians do when an adolescent wishes to risk his physical health and leave the hospital to attend the funeral of his late father? What if the young man's mother, and only remaining guardian, both supports and encourages such a decision? In this Ethics Rounds discussion, we examine the legality, morality, and safety of discharging a minor under such conditions., Competing Interests: POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose., (Copyright © 2018 by the American Academy of Pediatrics.)

We describe four patients who experienced optic neuritis (ON) and seizures and were found to have antibodies to myelin oligodendrocyte glycoprotein (MOG) in serum. The index case was a previously healthy 39-year-old man who developed steroid dependent ON and had a generalized seizure when steroids were tapered. He tested positive for antibodies to MOG. We have reviewed the charts of all 11 anti-MOG antibody positive patients in our practice and found that 4 patients, all of whom had experienced one or more episodes of ON, also had a generalized seizure during the course of their illness. In 2 patients - including the index case - seizure occurred during steroid taper and in 2 others at the time of an episode of acute disseminated encephalomyelitis (ADEM). Association of anti-MOG antibodies and relapsing demyelinating disorders of the central nervous system is increasingly recognized. Testing for anti-MOG antibodies should be considered in patients with optic neuritis and seizures, especially in those with who also have a history of ADEM., (Copyright © 2018 Elsevier B.V. All rights reserved.)

We investigated the relationship between retinal layers and normal-appearing white matter (WM) integrity in the brain of patients with relapsing-remitting multiple sclerosis (MS), using a combined diffusion tensor imaging and high resolution optical coherence tomography approach. Fifty patients and 62 controls were recruited. The patients were divided into two groups according to presence (n = 18) or absence (n = 32) of optic neuritis. Diffusion tensor data were analyzed with a voxel-wise whole brain analysis of diffusion metrics in WM with tract-based spatial statistics. Thickness measurements were obtained for each individual retinal layer. Partial correlation and multivariate regression analyses were performed, assessing the association between individual retinal layers and diffusion metrics across all groups. Region-based analysis was performed, by focusing on tracts associated with the visual system. Receiver operating characteristic (ROC) curves were computed to compare the biomarker potential for the diagnosis of MS, using the thickness of each retinal layer and diffusion metrics. In patients without optic neuritis, both ganglion cell layer (GCL) and inner plexiform layer thickness correlated with the diffusion metrics within and outside the visual system. GCL thickness was a significant predictor of diffusion metrics in the whole WM skeleton, unlike other layers. No association was observed for either controls or patients with a history of optic neuritis. ROC analysis showed that the biomarker potential for the diagnosis of MS based on the GCL was high when compared to other layers. We conclude that GCL integrity is a predictor of whole-brain WM disruption in MS patients without optic neuritis., (© 2018 Wiley Periodicals, Inc.)

Background: Quantitative assessment of optic nerve damage is important in the evaluation of optic neuritis (ON) and multiple sclerosis (MS)., Objective: To detect optic nerve damage using optical coherence tomography (OCT) and OCT angiography in MS., Methods: Peripapillary retinal nerve fibre layer (NFL) thickness, macular ganglion cell complex (GCC) thickness and Optic Nerve Head Flow Index (ONH-FI) were measured. The ONH-FI was defined as flow signal averaged over the optic disc. Diagnostic accuracy was evaluated by the area under the receiver-operating characteristics curve (AROC)., Results: Sixty-eight eyes of 45 MS participants and 55 eyes of 32 healthy controls (HCs) were analysed. Of MS eyes, 25 had a history of ON (MS+ON) and 43 didn't (MS-ON). MS-ON and MS+ON eyes had reductions in ONH-FI (p=0.031 and p=0.001, respectively), GCC thickness (p=0.245 and p<0.001, respectively), and NFL thickness (p=0.003 and p=0.024, respectively), compared with HCs. The highest AROC (0.940) was achieved by the logistic regression combination of all three variables, which was significantly higher than other variables (p=0.018)., Conclusion: MS produces both retinal structural loss and decreased ONH perfusion in MS eyes with and without history of ON. The combination of perfusion and structural measurements enhances detection of optic nerve damage in MS. OCT angiography may be a useful additional retinal marker in evaluation of ON in MS., Competing Interests: Competing interests: RIS, LL, XZ and DB have nothing to disclose. Oregon Health & Science University (OHSU) and DH, YJ and OT have a significant financial interest in Optovue, a company that may have a commercial interest in the results of this research and technology. These potential conflicts of interest have been reviewed and managed by OHSU., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Background and Purpose: Different biological and radiological biomarkers predict clinical conversion to multiple sclerosis (MS) after a clinically isolated syndrome (CIS). The aim was to explore their role in predicting the outcome of patients with optic neuritis (ON), a CIS considered to have a benign prognosis., Methods: Sixty-eight consecutive ON patients were followed prospectively. Magnetic resonance imaging (MRI) and cerebrospinal fluid studies including oligoclonal immunoglobulin G (IgG) bands (OCGBs), lipid-specific oligoclonal IgM bands (LS-OCMBs) and neurofilament light chain quantification were performed at disease onset. Conversion to clinically definite MS (CDMS) was monitored., Results: The mean time of follow-up of our series was 46.4 months. Twenty-five patients (36.7%) developed CDMS during follow-up. Neurofilament light chain levels did not predict clinical conversion. By contrast, an abnormal MRI increased the risk of CDMS [hazard ratio (HR) 12.5, P = 0.013]. The clearest association was found in patients with more than three T2 lesions. OCGBs also predicted the onset of CDMS (HR 21.3, P = 0.003) and LS-OCMBs were associated with a shorter time to CDMS (HR = 116.6, P < 0.001)., Conclusions: Magnetic resonance imaging and OCGBs predicted conversion to CDMS after an ON episode. In addition, LS-OCMBs identified the ON patients more likely to develop MS early. These results, applicable to the everyday clinical setting, may be of interest for therapeutic decisions., (© 2017 EAN.)

Objective The objective of this article is to evaluate advanced techniques of diffusion-weighted imaging (DWI) and apparent diffusion coefficient (ADC) measurements of the optic nerve in patients with optic neuritis. Methods In this prospective and institutional review board-approved trial, we examined 15 patients with acute visual loss and clinical signs of optic neuritis including thin-slice multi-shot segmented readout of long variable echo trains (rs-EPI, RESOLVE) DWI and reduced field-of view DWI using a parallel transmit system (rFOV-EPI). Conventional single-shot echo-planar DWI (ss-EPI) of the whole brain was available in 13 patients. Subjective image quality was compared using a four-point scale and objective ADC measurements were performed in comparison with the non-affected side. Results In the intraorbital segment, subjective image quality was significantly higher in rFOV-EPI (score 3.3 ± 0.8) compared with rs-EPI (score 2.1 ± 0.8) and ss-EPI (score 0.9 ± 0.8). Diagnosis was hampered in the canalicular segment ( n = 3) and the intracranial segment ( n = 1) in all applied DWI techniques. ADC measurements of the affected side differed significantly in all DWI sequences ss-EPI (sensitivity 54%, accuracy 77%), rs-EPI (sensitivity 71%, accuracy 86%), and rFOV-EPI (sensitivity 73%, accuracy 87%). Conclusion Optic neuritis in the intraorbital segment can be detected with high sensitivity without the need for contrast application. Using rFOV-EPI improves subjective image quality compared with rs-EPI and ss-EPI. Due to its higher spatial resolution, rFOV-EPI was the preferred technique in our study and can ensure the diagnosis in the intraorbital segment. However, artefacts occur in the canalicular and intracranial segment of the optic nerve, therefore contrast-enhanced T1-weighted images must still be considered as the gold standard.

Objective: We characterised the clinical course, treatment and outcomes in 59 patients with relapsing myelin oligodendrocyte glycoprotein (MOG) antibody-associated demyelination., Methods: We evaluated clinical phenotypes, annualised relapse rates (ARR) prior and on immunotherapy and Expanded Disability Status Scale (EDSS), in 218 demyelinating episodes from 33 paediatric and 26 adult patients., Results: The most common initial presentation in the cohort was optic neuritis (ON) in 54% (bilateral (BON) 32%, unilateral (UON) 22%), followed by acute disseminated encephalomyelitis (ADEM) (20%), which occurred exclusively in children. ON was the dominant phenotype (UON 35%, BON 19%) of all clinical episodes. 109/226 (48%) MRIs had no brain lesions. Patients were steroid responsive, but 70% of episodes treated with oral prednisone relapsed, particularly at doses <10 mg daily or within 2 months of cessation. Immunotherapy, including maintenance prednisone (P=0.0004), intravenous immunoglobulin, rituximab and mycophenolate, all reduced median ARRs on-treatment. Treatment failure rates were lower in patients on maintenance steroids (5%) compared with non-steroidal maintenance immunotherapy (38%) (P=0.016). 58% of patients experienced residual disability (average follow-up 61 months, visual loss in 24%). Patients with ON were less likely to have sustained disability defined by a final EDSS of ≥2 (OR 0.15, P=0.032), while those who had any myelitis were more likely to have sustained residual deficits (OR 3.56, P=0.077)., Conclusion: Relapsing MOG antibody-associated demyelination is strongly associated with ON across all age groups and ADEM in children. Patients are highly responsive to steroids, but vulnerable to relapse on steroid reduction and cessation., Competing Interests: Competing interests: Dr SR has received research funding from the National Health and Medical Research Council, the Petre Foundation and the Brain Foundation (Australia). Dr SM has received a scholarship from the National Health and Medical Research Council (Australia) and funding from the National Blood Authority IVIg grant. SB has received honoraria for attendance at advisory boards and travel sponsorship from Bayer-Schering, Biogen-Idec, Merck-Serono, Novartis and Sanofi-Genzyme, has received speakers honoraria from Biogen-Idec and Genzyme, is an investigator in clinical trials sponsored by Biogen-Idec, Novartis and Genzyme and was the recipient of an unencumbered research grant from Biogen-Idec. JL-S has accepted travel compensation from Novartis, Biogen and Merck-Serono. Her institution receives the honoraria for talks and advisory board commitment as well as research grants from Bayer Health Care, Biogen, Sanofi-Genzyme, Merck, Novartis and Teva. SR reports grants and personal fees from Sanofi-Genzyme, personal fees and departmental support from the Government of Australia, Baxter, Biogen, CSL and Merck; and departmental support from Novartis, outside the subject of the submitted work. Associate Professor FB has received research funding from the Star Scientific Foundation, The Trish Multiple Sclerosis Research Foundation, Multiple Sclerosis Research Australia and the National Health Medical Research Council (Australia). RD has received research funding from the Star Scientific Foundation, The Trish Multiple Sclerosis Research Foundation, Multiple Sclerosis Research Australia, the Petre Foundation and the National Health Medical Research Council (Australia). Dr RCD has received honoraria from Biogen-Idec as an invited speaker. Dr JLB has received compensation for education travel, honoraria for talks and advisory boards from Biogen, Teva, Merck-Serono, Sanofi-Genzyme, Novartis and Roche. Dr AC has received honoraria for attendance at advisory boards from Biogen and is an investigator in clinical trials sponsored by Biogen and Pfizer. Dr PC has accepted travel compensation from, Biogen and Merck Serono, and fellowship funding from Novartis/Biogen. Associate Professor CLF has received payment from Roche as a consultant. Dr MPM has received travel grants, speaking honoraria and unconditional research funding from Bayer, Biogen and Merck. Professor IES is supported by NHMRC Program Grant (1091593, 2016–2020) and Senior Practitioner Fellowship (1104831, 2016– 2020). IES serves on the editorial boards of Neurology and Epileptic Disorders; may accrue future revenue on a pending patent report: therapeutic compound; has received speakers honoraria from Athena Diagnostics, UCB, GSK, Eisai and Transgenomics; has received scientific advisory board honoraria from Nutricia and GSK, has received funding for travel from Athena Diagnostics, UCB and GSK and receives/has received research support from the NHMRC, ARC, NIH, Health Research Council of New Zealand, March of Dimes, the Weizmann Institute, CURE, US Department of Defense and the Perpetual Charitable Trustees. Dr EY is supported by an NHMRC Early Career Fellowship (APP1073323)., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Myelin oligodendrocyte glycoprotein is a protein exclusively expressed on the surface of oligodendrocytes and myelin in the central nervous system. Antibodies against myelin oligodendrocyte glycoprotein were initially detected in children with demyelinating syndromes, and more recently reported in a broad spectrum of central nervous system demyelinating diseases in adults, including neuromyelitis optica spectrum disorders and bilateral optic neuritis. Patients with myelin oligodendrocyte glycoprotein antibody-associated demyelination appear to have unique clinical and radiological features. To the best of our knowledge a series of Italian patients with optic neuritis and positivity to myelin oligodendrocyte glycoprotein antibodies has not yet been reported and the paper on myelin oligodendrocyte glycoprotein antibodies are more focused on clinical features, diagnosis and outcome than on the radiological appearance, so we want to retrospectively report magnetic resonance imaging features of a group of eight patients, who came to our Ophthalmologic Emergency Department for optic neuritis and were found seropositive for myelin oligodendrocyte glycoprotein antibodies, comparing our data with the findings described in the literature.

Background: Optic neuritis (ON) is a focal demyelinating event, which may evolve into multiple sclerosis (MS)., Objective: To study MRI characteristics in the acute phase of the first ON episode., Methods: A prospective population-based study was performed on 31 patients with a first episode of acute ON with a one year follow-up. MRI, clinical evaluation, and detection of aquaporin-4 (AQP4)-IgG and myelin oligodendrocyte glycoprotein (MOG)-IgG was undertaken. For lesion characterization on MRI the optic nerves were divided into three segments: intra-orbital (IO), canalicular (CAN) and chiasmal (CHI)., Results: Lesions of the optic nerve were observed in 80.6%(25/31), with IO location in 48%(12/25), CAN in 8% (2/25) and both IO and CAN in 44%(11/25). Patients who converted to MS had lesions located at IO in 77%(10/13), whereas the group with isolated ON had IO and CAN in 73% (8/11), p = 0.003. Brain lesions were observed in 84% (21/25) at onset of ON; 62%(13/25) progressed to MS with more frequent location in brainstem (p = 0.030) and lesions in periventricular areas (p = 0.015). Spinal cord lesions were detected only in patients who progressed to MS (p = 0.002). MOG-IgG was detected in one patient with an optic nerve lesion located at IO and CAN. Serum AQP4-IgG was detected in none. Follow-up MRI showed progression in optic nerve lesions in 55% (11/20) patients., Conclusions: Specific location of optic nerve and brain lesions and the presence of spinal cord lesions in the acute phase of the first ON episode facilitated an MS diagnosis. The extension of optic nerve lesions following ON suggests a long-term progressive degeneration as an important element of ON pathology., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Background: Inner retinal layer (IRL) atrophy is a potential biomarker for neurodegeneration in multiple sclerosis (MS)., Objective: To investigate the relationship between cognitive impairment and IRL atrophy in MS., Methods: Cross-sectional study design, including 217 patients and 59 healthy controls. Subjects were investigated clinically, underwent retinal optical coherence tomography (OCT) and comprehensive cognitive assessments. The association between these modalities was evaluated by regression analyses., Results: Of the patients, 44.2% were cognitively impaired. In the absence of multiple sclerosis-associated optic neuritis (MSON), cognitively impaired patients had a significantly lower mean peripapillary retinal nerve fiber layer (pRNFL, Δ: 8.13 µm, p < 0.001) and mean macular ganglion cell-inner plexiform layer (mGCIPL, Δ: 11.50 µm, p < 0.001) thickness compared to cognitively preserved patients. There was a significant association between the presence of cognitive impairment and pRNFL (odds ratio (OR): 1.11, 95% confidence interval (CI): 1.04-1.18, p = 0.001) and mGCIPL (OR = 1.11, 95% CI = 1.05-1.18, p < 0.001) atrophy. This association was masked by the severe IRL atrophy seen following MSON., Conclusion: The strong relationship between cognitive impairment across multiple cognitive domains and atrophy of the pRNFL and mGCIPL in patients who never suffered from MSON suggests that OCT is useful in assessing central nervous system neurodegeneration in MS.

Background: In 2016, the Magnetic Resonance Imaging in Multiple Sclerosis (MAGNIMS) network proposed modifications to the MRI criteria to define dissemination in space (DIS) and time (DIT) for the diagnosis of multiple sclerosis in patients with clinically isolated syndrome (CIS). Changes to the DIS definition included removal of the distinction between symptomatic and asymptomatic lesions, increasing the number of lesions needed to define periventricular involvement to three, combining cortical and juxtacortical lesions, and inclusion of optic nerve evaluation. For DIT, removal of the distinction between symptomatic and asymptomatic lesions was suggested. We compared the performance of the 2010 McDonald and 2016 MAGNIMS criteria for multiple sclerosis diagnosis in a large multicentre cohort of patients with CIS to provide evidence to guide revisions of multiple sclerosis diagnostic criteria., Methods: Brain and spinal cord MRI and optic nerve assessments from patients with typical CIS suggestive of multiple sclerosis done less than 3 months from clinical onset in eight European multiple sclerosis centres were included in this retrospective study. Eligible patients were 16-60 years, and had a first CIS suggestive of CNS demyelination and typical of relapsing-remitting multiple sclerosis, a complete neurological examination, a baseline brain and spinal cord MRI scan obtained less than 3 months from clinical onset, and a follow-up brain scan obtained less than 12 months from CIS onset. We recorded occurrence of a second clinical attack (clinically definite multiple sclerosis) at months 36 and 60. We evaluated MRI criteria performance for DIS, DIT, and DIS plus DIT with a time-dependent receiver operating characteristic curve analysis., Findings: Between June 16, 1995, and Jan 27, 2017, 571 patients with CIS were screened, of whom 368 met all study inclusion criteria. At the last evaluation (median 50·0 months [IQR 27·0-78·4]), 189 (51%) of 368 patients developed clinically definite multiple sclerosis. At 36 months, the two DIS criteria showed high sensitivity (2010 McDonald 0·91 [95% CI 0·85-0·94] and 2016 MAGNIMS 0·93 [0·88-0·96]), similar specificity (0·33 [0·25-0·42] and 0·32 [0·24-0·41]), and similar area under the curve values (AUC; 0·62 [0·57-0·67] and 0·63 [0·58-0·67]). Performance was not affected by inclusion of symptomatic lesions (sensitivity 0·92 [0·87-0·96], specificity 0·31 [0·23-0·40], AUC 0·62 [0·57-0·66]) or cortical lesions (sensitivity 0·92 [0·87-0·95], specificity 0·32 [0·24-0·41], AUC 0·62 [0·57-0·67]). Requirement of three periventricular lesions resulted in slightly lower sensitivity (0·85 [0·78-0·90], slightly higher specificity (0·40 [0·32-0·50], and similar AUC (0·63 [0·57-0·68]). Inclusion of optic nerve evaluation resulted in similar sensitivity (0·92 [0·87-0·96]), and slightly lower specificity (0·26 [0·18-0·34]) and AUC (0·59 [0·55-0·64]). AUC values were also similar for DIT (2010 McDonald 0·61 [0·55-0·67] and 2016 MAGNIMS 0·61 [0·55-0·66]) and DIS plus DIT (0·62 [0·56-0·67] and 0·64 [0·58-0·69])., Interpretation: The 2016 MAGNIMS criteria showed similar accuracy to the 2010 McDonald criteria in predicting the development of clinically definite multiple sclerosis. Inclusion of symptomatic lesions is expected to simplify the clinical use of MRI criteria without reducing accuracy, and our findings suggest that needing three lesions to define periventricular involvement might slightly increase specificity, suggesting that these two factors could be considered during further revisions of multiple sclerosis diagnostic criteria., Funding: UK MS Society, National Institute for Health Research University College London Hospitals Biomedical Research Centre, Dutch MS Research Foundation., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Purpose: To analyze the changes in retinal nerve fiber layer (RNFL) in eyes with and without prior history of optic neuritis (ON) of patients with multiple sclerosis (MS) after a 5-year time period (2010-2015) using optical coherence tomography., Methods: The RNFL thickness of 114 eyes of 57 MS patients and 40 eyes of 20 healthy subjects were measured in year 2010 and year 2015. Measurements were made separately in twelve sectors around the optic nerve head. Statistical comparisons were made with the obtained data., Results: Progressive RNFL thinning occurs with time in both MS patients (regardless the eye had history of ON or not) and in normal subjects. The baseline mean RNFL thickness in ON eyes of MS patients (year 2010) was 74.2 ± 15.7µm and five years later was 68.7 ± 12.2µm. The baseline mean RNFL thickness in eyes without ON of MS patients was 90.0 ± 11.1µm and 84.7 ± 10.3µm five years later. The median RNFL thickness reduction was 3.5µm for ON eyes, 4.7µm for eyes without ON, and 2.2µm for control eyes. The RNFL thickness reduction rate was similar in eyes with history of ON that in those with no history of ON. On the contrary, the MS group had a significantly higher rate of reduction than the control group., Conclusions: MS patients have thinner RNFL than normal controls, regardless their eyes had past episodes of ON or not. Eyes of MS patients lose their axons in a similar fashion regardless they had history of ON or not. Although ON causes RNFL loss, once resolved it does not influence the rate of RNFL loss in MS patients., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Objectives: To assess the contributions of cortico-juxtacortical and corpus callosum lesions to multiple sclerosis diagnosis and to compare the value of ≥1 vs ≥3 periventricular lesions in clinically isolated syndromes (CIS)., Methods: Step 1: We evaluated lesion topography classifications in 657 patients with CIS with stepwise Cox proportional hazards regression models considering second attack as the outcome. Step 2: We established 2 dissemination in space (DIS) versions according to the periventricular lesion cutoffs of ≥1 and ≥3 and assessed their performance at 10 years with second attack as the outcome, first individually and then combined with dissemination in time (DIT) in all cases (n = 326), by age, and by CIS topography., Results: Step 1: The models (hazard ratios [95% confidence interval]) favored ≥1 over ≥3 periventricular lesions (2.5 [1.7-3.6]) and cortico-juxtacortical over juxtacortical lesions (1.4 [1.0-1.8]). Callosal lesions were not selected. Step 2: DIS specificity with ≥1 periventricular lesions was slightly lower than with ≥3 (59.1 vs 61.4) and the same after adding DIT (88.6). Regarding age, ≥3 periventricular lesions improved DIS specificity over ≥1 lesions in the 40-49 years of age bracket (66.7 vs 58.3). This difference disappeared when adding DIT (83.3). Optic neuritis had a similar pattern when evaluating CIS topographies., Conclusions: Our results comply with the Magnetic Resonance Imaging in Multiple Sclerosis (MAGNIMS) consensus recommendation of combining cortical and juxtacortical lesions into a single term when possible. Concerning periventricular lesions, maintaining the current ≥1 cutoff in the McDonald criteria does not compromise specificity in typical CIS cases, but attention should be paid to older patients or optic neuritis cases., (Copyright © 2017 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)

Background: Optic neuritis (ON) is often associated with multiple sclerosis (MS). Early diagnosis is critical to optimal patient management., Objective: To estimate the incidence of acute ON and the rates of conversion to MS and antibody-mediated ON., Method: Population-based prospective study was performed in patients with ON from three ophthalmological departments and 44 practicing ophthalmologists from 2014 to 2016. Ophthalmological and neurological examination, magnetic resonance imaging (MRI), determination of aquaporin-4(AQP4)-IgG and myelin-oligodendrocyte glycoprotein (MOG)-IgG were investigated blindly., Results: In all, 63 patients were evaluated and 51 fulfilled the criteria for ON. All were Caucasian, with female:male ratio of 2.2:1 and a median age of 38 years (16-66); 44 (86%) had a single episode of ON (four bilateral), while 7/51 (14%) had recurrent ON. The overall age-specific incidence was 3.28 (2.44-4.31) per 100,000 person years, 2.02 for men and 4.57 for women. At follow-up, 20 patients met the diagnostic criteria for MS, MRI lesions disseminated in space and time in 17/20 patients. AQP4-IgG was detected in none, MOG-IgG was detected in two patients., Conclusion: The prospective incidence of ON was estimated. MRI enabled a diagnosis of MS in a subgroup of patients. Antibody-mediated ON with specificity for MOG was detected in 4% of cases.

Background and Purpose: Multiple sclerosis-associated optic neuritis (MSON) causes atrophy of the inner retinal layers, which can be quantified by optical coherence tomography. It has been suggested that the inter-eye percentage difference (IEPD) of atrophy may be of diagnostic value in MSON., Methods: This was a prospective, cross-sectional study in patients with multiple sclerosis and healthy controls (HCs). Spectral-domain optical coherence tomography of both eyes was performed, followed by automated retinal layer segmentation of the peri-papillary retinal nerve fibre layer (pRNFL) and macular ganglion cell and inner plexiform layer (mGCIPL). Receiver operator characteristics curves were plotted and the area under the curve was calculated for group comparisons of the IEPD of the pRNFL and mGCIPL., Results: There were 39 patients with bilateral MSON, 62 patients with unilateral MSON, 106 patients without MSON and 63 HCs. Diagnostic accuracy (area under the curve) of the IEPD was 0.73-0.86 for the pRNFL and 0.75-0.94 for the mGCIPL. The diagnostic sensitivity of the mGCIPL IEPD was 70% with a specificity of 97% for distinguishing unilateral MSON from HCs. For the comparison of bilateral MSON with HCs, sensitivity was 86% with a specificity of 97%., Conclusions: The IEPD of the pRNFL, and more particularly the IEPD of the mGCIPL, is a useful diagnostic measure for MSON. The IEPD is a dimensionless unit and may therefore contribute to overcome device and proprietary segmentation algorithm limitations., (© 2017 EAN.)

A 64-year-old woman was admitted to our hospital owing to decreased visual acuity and visual field defect. She had a similar history of decreased visual acuity and received steroid therapy 10 years ago. Brain MRI revealed gadolinium-enhancement in the sheath of the optic nerve, called "tram-track" and "doughnut" signs. Optic perineuritis (OPN) was diagnosed on the basis of her clinical manifestations, which improved on treatment with high-dose methylprednisolone (mPSL). However, clinical manifestations relapsed 10 days post-discharge; hence, she was re-admitted. She was re-administered high-dose mPSL and subsequent oral administration of prednisolone. She had no relapse or recurrence for the last 2 years. We reviewed studies involving Japanese patients with OPN, including 17 idiopathic and 14 secondary cases and found that 43% of patients had recurrences and 30% of patients had poor outcome including severe residuals of visual acuity. Secondary OPN occurred owing to various diseases manifesting generalized systematic inflammation. Timely and suitable treatment was very important for clinical favorable outcomes in OPN.

Background: Angiogenesis and vascular endothelial growth factor (VEGF) have recently been implicated in animal and clinical models of radiation-induced optic nerve, retinal, and brain necrosis. Although there are isolated case reports of anti-VEGF therapy with bevacizumab for management of radiation-induced brain necrosis, there are little data defining its role in radiation-induced optic nerve damage., Patients and Methods: This study included patients with a sellar-suprasellar tumor who underwent intensity-modulated or Gamma Knife radiotherapy and developed radiation-induced optic neuritis (RION) refractory to 3 weeks of glucocorticoid therapy who received bevacizumab 5 mg/kg intravenously as initial dose, followed by subsequent doses of 10 mg/kg., Results: Here we report 3 patients with sellar-suprasellar lesions undergoing conventional radiation therapy (2 cases) or Gamma Knife surgery (1 case) who had benefitted from anti-VEGF therapy following radiation-induced optic nerve damage., Conclusions: Early bevacizumab therapy in steroid-refractory RION shows gratifying results., (Copyright © 2017 Elsevier Inc. All rights reserved.)

In recent years, not only the incidence of brain demyelinating disease has increased, but also it seems that the world is facing new forms of autoimmune diseases of the brain. Distinguishing these diseases from each other is very important, since each requires a different treatment. The new criteria that were put forward in 2015 were meant to pave the way for better diagnosis of these diseases called neuromyelitis optica spectrum disease (NMOSD). However, too much emphasis on the criteria based on the convergence and association of radiological findings with the clinical symptoms actually causes confusion in the diagnosis. Here, the case of a 16-year-old child suffering from optic neuritis has been discussed. Her cervical magnetic resonance imaging (MRI) revealed longitudinal extensive transverse myelitis (LETM); however, the patient had no symptoms of the spinal cord's involvement. According to the 2015 criterion, the diagnosis of NMOSD cannot be accepted for this patient. Therefore, this case report emphasizes on the modification of the existing criterion., (Copyright © 2017 Elsevier B.V. All rights reserved.)

In optic neuritis (ON) inflammation precedes onset of demyelination and axonal loss. The anti-inflammatory properties of corticosteroids may be most effective in the early inflammatory phase, but rapid patient recruitment remains a logistic challenge. The aim of the study was to review the effect of time to initiation of treatment on visual outcome in recurrent ON. A retrospective case note review of patients known to our centre with recurrent ON. The primary clinical outcome was change of best corrected high contrast visual acuity (BCVA). The secondary outcome was the change of optical coherence tomography (OCT) thickness of the peripapillary retinal nerve fibre layer (pRNFL) and macular ganglion cell layer (mGCL) from baseline and after a minimum of 3months following the episode of recurrent ON. Of 269 patients with a previous episode of ON, 54 experienced recurrent ON. In total 40 OCT documented episodes of relapsing ON were captured in 19 patients. Treatment within <2days led to better recovery of the BCVA (+0.02) and mGCL (-2.4µm) if compared to delayed treatment (BCVA -0.2, p=0.036, mGCL -25.6µm, p=0.019) or no corticosteroids treatment (BCVA -0.2, p=0.045, GCL -5.0µm, p=0.836). These data suggest a beneficial effect of hyperacute corticosteroid treatment. A pragmatic approach for a prospective treatment trial should consider patients with recurrent ON for logistic reasons., (Copyright © 2017 Elsevier B.V. All rights reserved.)