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Background and Purpose: Low-field 64 mT portable brain MRI has recently shown diagnostic promise for MS. This study aimed to evaluate the utility of portable MRI (pMRI) in assessing dissemination in space (DIS) in patients presenting with optic neuritis and determine whether deploying pMRI in the MS clinic can shorten the time from symptom onset to MRI., Materials and Methods: Newly diagnosed patients with optic neuritis referred to a tertiary academic MS center from July 2022 to January 2024 underwent both point-of-care pMRI and subsequent 3T conventional MRI (cMRI). Images were evaluated for periventricular (PV), juxtacortical (JC), and infratentorial (IT) lesions. DIS was determined on brain MRI per 2017 McDonald criteria. Test characteristics were computed by using cMRI as the reference. Interrater and intermodality agreement between pMRI and cMRI were evaluated by using the Cohen κ. Time from symptom onset to pMRI and cMRI during the study period was compared with the preceding 1.5 years before pMRI implementation by using Kruskal-Wallis with post hoc Dunn tests., Results: Twenty patients (median age: 32.5 years [interquartile range {IQR}, 28-40]; 80% women) were included, of whom 9 (45%) and 5 (25%) had DIS on cMRI and pMRI, respectively. Median time interval between pMRI and cMRI was 7 days (IQR, 3.5-12.5). Interrater agreement was very good for PV (95%, κ = 0.89), and good for JC and IT lesions (90%, κ = 0.69 for both). Intermodality agreement was good for PV (90%, κ = 0.80) and JC (85%, κ = 0.63), and moderate for IT lesions (75%, κ = 0.42) and DIS (80%, κ = 0.58). pMRI had a sensitivity of 56% and specificity of 100% for DIS. The median time from symptom onset to pMRI was significantly shorter (8.5 days [IQR 7-12]) compared with the interval to cMRI before pMRI deployment (21 days [IQR 8-49], n  = 50) and after pMRI deployment (15 days [IQR 12-29], n  = 30) (both P < .01). Time from symptom onset to cMRI in those periods was not significantly different ( P  = .29)., Conclusions: In patients with optic neuritis, pMRI exhibited moderate concordance, moderate sensitivity, and high specificity for DIS compared with cMRI. Its integration into the MS clinic reduced the time from symptom onset to MRI. Further studies are warranted to evaluate the role of pMRI in expediting early MS diagnosis and as an imaging tool in resource-limited settings., (© 2024 by American Journal of Neuroradiology.)

Purpose: The retinal microvascular network plays a crucial role in inflammatory injury in paediatric optic neuritis (PON) with serum MOG antibody positivity (MOG + PON). This study compared retinal microvascular densities and structural alterations in MOG + PON eyes with paediatric isolated optic neuritis (PION) eyes and followed up with the final best-corrected visual acuity (BCVA) after 6 months., Methods: A total of 29 children (52 eyes) with PON, including 15 MOG + PON cases (28 eyes), 6 PION cases (10 eyes), 2 neuromyelitis optica spectrum disorders associated PON(NMOSD-PON) cases (4 eyes), 6 MOG-associated disease (MOGAD) patients without ON-affected eyes (MOG + NPON) cases (10 eyes) and age- and gender-matched healthy controls (HCs) underwent superficial/deep retinal angiography density (SAD/DAD) by optical coherence tomography angiography (OCTA). Their BCVAs were followed up until 6 months after PON onsets., Results: MOG + PON cases had better final BCVAs than PION and NMOSD-ON. MOG + PON (35.7 ± 10.3 %) and PION (40.1 ± 10.3 %) eyes experienced severe SAD reductions in contrast to MOGAD+NPON (48.7 ± 5.2 %) and HCs eyes (55.6 ± 8.2 %). However, DAD in MOG + PON eyes (48.5 ± 9.2 %) and MOG + NPON eyes (53.1 ± 3.3 %) increased compared to HC eyes (45.7 ± 9.6 %; p = 0.028 and 0.009, respectively). SAD reduction occurred in acute PON and was detected as early as 2 weeks after PON onset., Conclusions: MOG + PON eyes had better final BCVAs than PION eyes, which displayed superficial retinal microvascular perfusion reductions and deep microvascular perfusion increases. SAD could be a sensitive surrogate for PON attacks in children with MOGAD., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background and Objectives: The 2022 International Consortium for Optic Neuritis diagnostic criteria for optic neuritis (ON) include optical coherence tomography (OCT). The diagnostic value of intereye difference (IED) metrics is high for ON in patients with multiple sclerosis and aquaporin-4 antibody seropositive neuromyelitis optica spectrum disorders, but unknown in myelin oligodendrocyte glycoprotein antibody-associated ON (MOG-ON)., Methods: A multicenter validation study was conducted on the published IED cutoff values (>4% or >4 μm in the macular ganglion cell and inner plexiform layer [mGCIP] or >5% or >5 μm in the peripapillary retinal nerve fiber layer [pRNFL]) in individuals with MOG-ON and age-matched and sex-matched healthy controls (HCs). Structural data were acquired with Spectralis spectral-domain OCT >6 months after ON. We calculated sensitivity, specificity, and receiver operating characteristics for both intereye percentage (IEPD) and absolute difference (IEAD)., Results: A total of 66 individuals were included (MOG-ON N = 33; HCs N = 33). ON was unilateral in 20 and bilateral in 13 subjects. In the pooled analysis, the mGCIP IEPD was most sensitive (92%), followed by the mGCIP IEAD (88%) and pRNFL (84%). The same pattern was found for the specificity (mGCIP IEPD 82%, IEAD 82%; pRNFL IEPD 82%, IEAD 79%).In subgroup analyses, the diagnostic sensitivity was higher in subjects with unilateral ON (>99% for all metrics) compared with bilateral ON (61%-78%)., Discussion: In individuals with MOG-ON, the diagnostic accuracy of OCT-based IED metrics for ON was high, especially of mGCIP IEPD., Classification of Evidence: This study provides Class III evidence that the intereye difference on OCT can distinguish between those with MOG and normal controls.

Background and Objectives: Recovery of vision after acute optic neuritis (AON) is critical to improving the quality of life of people with demyelinating diseases. The objective of the study was to prospectively assess the changes in visual acuity, retinal layer thickness, and cortical visual network in patients with AON to identify the predictors of permanent visual disability., Methods: We studied a prospective cohort of 88 consecutive patients with AON with 6-month follow-up using high and low-contrast (2.5%) visual acuity, color vision, retinal thickness from optical coherence tomography, latencies and amplitudes of multifocal visual evoked potentials, mean deviation of visual fields, and diffusion-based structural (n = 53) and functional (n = 19) brain MRI to analyze the cortical visual network. The primary outcome was 2.5% low-contrast vision, and data were analyzed with mixed-effects and multivariate regression models., Results: We found that after 6 months, low-contrast vision and quality of vision remained moderately impaired. The thickness of the ganglion cell layer at baseline was a predictor of low-contrast vision 6 months later (ß = 0.49 [CI 0.11-0.88], p = 0.012). The structural cortical visual network at baseline predicted low-contrast vision, the best predictors being the betweenness of the right parahippocampal cortex (ß = -036 [CI -0.66 to 0.06], p = 0.021), the node strength of the right V3 (ß = 1.72 [CI 0.29-3.15], p = 0.02), and the clustering coefficient of the left intraparietal sulcus (ß = 57.8 [CI 12.3-103.4], p = 0.015). The functional cortical visual network at baseline also predicted low-contrast vision, the best predictors being the betweenness of the left ventral occipital cortex (ß = 8.6 [CI: 4.03-13.3], p = 0.009), the node strength of the right intraparietal sulcus (ß = -2.79 [CI: -5.1-0.4], p = 0.03), and the clustering coefficient of the left superior parietal lobule (ß = 501.5 [CI 50.8-952.2], p = 0.03)., Discussion: The assessment of the visual pathway at baseline predicts permanent vision disability after AON, indicating that damage is produced early after disease onset and that it can be used for defining vision impairment and guiding therapy.

Aim: to describe and analyze peripapillary microvascular changes in eyes with optic neuropathies using optical coherence tomography angiography (OCTA)., Methods: In this cross-sectional observational study, 63 eyes of 48 patients with different causes of optic neuropathy and 36 healthy control eyes were evaluated by optical coherence tomography (OCT) and OCTA (Topcon DRI OCT; Triton) between January 2018 and December 2018 at the Fattouma Bourguiba ophthalmology department in Monastir., Results: Vascular changes were more frequent in acute non arteritic anterior ischemic optic neuropathy (NAION) than in optic neuritis. Eyes with optic atrophy had capillary rarefaction corresponding to the area of thinning of the peripapillary optic fiber layer (RNFL). The peripapillary vascular density (PVD) was lower (p=0.036) in case of optic atrophy compared to normal eyes. For non arteritic ischemic optic neuropathy and for chronic retrobulbar optic neuritis (NORB), a positive correlation between visual acuity and PVD was observed (p<0.05). An inversely proportional correlation between the PVD and the duration of evolution was noted. In the multivariate study, high blood pressure was a systemic factor correlated with peripapillary microvascular damages., Conclusion: OCTA showed a reduction in PVD and greater vascular changes in acute non-arteritic ischemic optic neuropathy than in edematous optic neuritis. At the atrophic stage, the PVD was reduced. Hypertension was an independent factor correlated with peripapillary microvascular damages.

Background and Objectives: Slow-burning inflammation at the edge, and chronic demyelination at the core, of established multiple sclerosis (MS) lesions are potential mediators of disease progression. However, their relative contribution to progressive axonal damage has not been explored. Therefore, in this study, we investigated the comparative contribution of slow-burning inflammation and chronic demyelination to axonal attrition within MS lesions by measuring progressive tissue rarefaction. In addition, we use the visual system as a model to investigate the effect of chronic demyelination on the acceleration of axonal death in a sub-group of patients with unilateral optic neuritis., Methods: Pre- and post-gadolinium 3D-T1, 3D FLAIR, diffusion tensor images, Optical Coherence tomography and multifocal visual evoked potentials were acquired from 52 relapsing-remitting MS patients who completed at least 5 years follow-up. Lesion expansion was measured using custom software, and the rate of tissue rarefication inside lesion core was assessed by measuring increase of normalized mean diffusivity (nMD). Axonal loss was also examined in eyes with severe optic nerve demyelination., Results: Among the 361 lesions analyzed, 104 were expanding (a minimum of 4 % expansion per year) and 257 were stable. Expanding lesions showed a significantly higher rate of progressive tissue rarefication inside lesion (1.12 % per year) core compared to stable lesions (0.21 % per year, p = 0.01). The magnitude of nMD change was significantly correlated with the rate of lesion expansion (r = 0.4, p < 0.001). Analysis of retinal ganglion cells in eyes with severe optic nerve demyelination (Inter-eye latency delay of >10 ms) revealed a similar rate of axonal loss (0.19 %) to the degree of tissue rarefaction observed in stable lesions (0.21 %)., Discussion: The results of the study suggest that the slow-burning inflammation at the lesion's edge (as measured by lesion expansion), is likely to have a greater impact on tissue damage (as measured by nMD change), when compared to stable chronically demyelinated lesions. The similar modest degree of tissue damage was also observed in chronically demyelinated fibers of the optic nerve., Competing Interests: Declaration of competing interest Authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (Copyright © 2024. Published by Elsevier B.V.)

Objectives: Optic neuritis is a common clinical presentation in patients suffering from multiple sclerosis (MS). Even though optic neuritis is not part of the MS diagnostic criteria, the diagnosis and consideration of differential diagnoses are important in clinical routine. For the evaluation of the optic nerves with MRI, T2-weighted images with fat suppression, known as short tau inversion recovery sequences (STIR), are often used. Besides that, double inversion recovery (DIR) sequences are being used increasingly in MS patients, especially to determine cortical lesions. The Aim of this study was to evaluate the 3D-DIR for the detection of lesions in the optic nerves in MS patients., Methods: MR examinations of 45 MS-patients containing both STIR and DIR images were independently assessed by two neuroradiologic experienced radiologists, blinded to clinical data. A third neuroradiologic, an experienced radiologist, evaluated the images together, also considering clinical data. These results were considered ground truth and statistically compared to the results of the single readings. To objectify our findings, ROI measurements of affected and unaffected optic nerve segments were made, and a contrast ratio (CR) was calculated., Result: DIR images are statistically equivalent to STIR images concerning the detection of lesions in the optic nerve (p < 0.001). The sensitivity of DIR images (84.7 %) and STIR images (77 %), as well as the specificity (92.2 % and 91.2 %), are comparable. The interrater reliability was substantial for both sequences (κ = 0,73) as well as separated for the STIR images (κ = 0.744) and the DIR images (κ = 0.707). The objective analysis revealed significantly higher CRs in DIR images (p < 0.001)., Conclusion: 3D DIR images showed similar sensitivity and specificity for detecting optic nerve lesions in comparison to dedicated 2D images of the optic nerve. When 3D DIR images are part of the routine scan protocol for evaluating MS patients, additional 2D imaging of the optic nerve is no longer necessary., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: Multiple sclerosis (MS) is an autoimmune demyelinating disease of the central nervous system with neuroaxonal damage. It is the principal driver of non-traumatic disability in young adults. Visual symptoms are common and optic neuritis (ON) may be the revealing feature in up to 30% of cases. Structural optical coherence tomography (OCT) represents a biomarker of central nervous system neurodegeneration in MS. OCT-angiography (OCT-A) is a noninvasive tool allowing the study of retinal vasculature and the detection of microvascular damage in neuro-retinal diseases. In this study, we aimed to assess structural and microvascular retinal changes in patients with MS with and without ON and to correlate the findings with visual function and MS disability., Methods: We conducted a cross-sectional study including patients diagnosed with MS according to the 2017 McDonald criteria. All patients underwent complete neurological examination with evaluation of the Expanded Disability Status Scale (EDSS) and the Multiple Sclerosis Severity Score (MSSS) and an ophthalmological examination including OCT and OCT-A. Patients were compared with age- and sex-matched healthy subjects. The primary endpoints were assessment of retinal nerve fiber layer (RNFL) thickness, ganglion cell layer (GCL+), and ganglion cell complex (GCL++) thicknesses on OCT. Vascular densities in the superficial capillary plexus (SCP), deep capillary plexus (DCP), and choriocapillaris (CC) were assessed on OCT-A, as well as central avascular zone (CAZ) parameters, lacunarity and fractal dimension., Results: A total of 160 MS eyes with and without a previous history of ON and 64 age- and gender-matched healthy eyes were analyzed. Among 160 eyes with MS, 69 had a history of ON. We observed a decrease in RNFL and GCL++ thickness in all 12 quadrants in MS patients when compared to healthy controls. Multivariate analysis by linear regression noted a significant correlation for temporal GCL++ and inferonasal RNFL thickness that were decreased in the MS group. A greater decrease in retinal layers thickness was identified in MS patients with a history of ON. On OCT-A, vascular density in (SCP) was significantly reduced in the MS group (P<0.002). A significant correlation between RNFL thickness and retinal vascular density was found but only in less than half of the hourly quadrants. A significant correlation was noted between visual acuity and CC density (P<0.0001). We also noted an inverse correlation between EDSS scores and CC density (P=0.02 and r=-0.275) and between MSSS and RNFL/GCL++ thicknesses., Conclusions: RNFL and GCL++ layers were thinner in MS patients with a history of ON and were reversely correlated with disease severity. Moreover, retinal vascular changes were observed in MS even in eyes without ON, and CC was reversely correlated with visual function and current disability. Thus, structural OCT coupled with OCT-A could represent a noninvasive and dynamic biomarker of MS severity and progression., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

Neuromyelitis optica spectrum disorder (NMOSD), also known as Devic disease, is an autoimmune central nervous system disorder in humans that commonly causes inflammatory demyelination in the optic nerves and spinal cord. Inflammation in the optic nerves is termed optic neuritis (ON). ON is a common clinical presentation; however, it is not necessarily present in all NMOSD patients. ON in NMOSD can be relapsing and result in severe vision loss. To the best of our knowledge, no study utilises deep learning to classify ON changes on MRI among patients with NMOSD. Therefore, this study aims to deploy eight state-of-the-art CNN models (Inception-v3, Inception-ResNet-v2, ResNet-101, Xception, ShuffleNet, DenseNet-201, MobileNet-v2, and EfficientNet-B0) with transfer learning to classify NMOSD patients with and without chronic ON using optic nerve magnetic resonance imaging. This study also investigated the effects of data augmentation before and after dataset splitting on cropped and whole images. Both quantitative and qualitative assessments (with Grad-Cam) were used to evaluate the performances of the CNN models. The Inception-v3 was identified as the best CNN model for classifying ON among NMOSD patients, with accuracy of 99.5%, sensitivity of 98.9%, specificity of 93.0%, precision of 100%, NPV of 99.0%, and F1-score of 99.4%. This study also demonstrated that the application of augmentation after dataset splitting could avoid information leaking into the testing datasets, hence producing more realistic and reliable results., (© 2024 IOP Publishing Ltd. All rights, including for text and data mining, AI training, and similar technologies, are reserved.)

The optic nerve is frequently involved in multiple sclerosis (MS). However, MRI of the optic nerve is considered optional in the differential diagnosis of optic neuropathy symptoms either at presentation or in established MS. In addition, unlike spinal cord imaging in comparable scenarios, no role is currently recommended for optic nerve MRI in patients presenting with optic neuritis for its confirmation, to plan therapeutic strategy, within the MS diagnostic framework, nor for the detection of subclinical activity in established MS. In this article, evidence related to these 3 aspects will be summarized and gaps in knowledge will be highlighted, including (1) the acquisition challenges and novel sequences that assess pathologic changes within the anterior visual pathways; (2) the clinical implications of quantitative magnetic resonance studies of the optic nerve, focusing on atrophy measures, magnetization transfer, and diffusion tensor imaging; and (3) the relevant clinical studies performed to date. Finally, an algorithm for the application of optic nerve MRI will be proposed to guide future studies aimed at addressing our knowledge gaps.

Optic neuritis is a common feature in multiple sclerosis and in 2 other autoimmune demyelinating disorders such as aquaporin-4 IgG antibody-associated neuromyelitis optica spectrum disorder and myelin oligodendrocyte glycoprotein antibody-associated disease. Although serologic testing is critical for differentiating these different autoimmune-mediated disorders, MR imaging, which is the preferred imaging modality for assessing the optic nerve, can provide valuable information, suggesting a specific diagnosis and guiding the appropriate serologic testing., Competing Interests: Disclosure Àlex Rovira serves/ed on scientific advisory boards for Novartis, Sanofi-Genzyme, Synthetic MR, TensorMedical, Roche, and Biogen, and has received speaker honoraria from Bayer, Sanofi-Genzyme, Merck-Serono, Teva Pharmaceutical Industries Ltd, Novartis, Roche, Bristol-Myers and Biogen, is CMO and co-founder of TensorMedical, and receives research support from Fondo de Investigación en Salud (PI19/00950 and PI22/01589) from Instituto de Salud Carlos III, Spain. Angela Vidal-Jordana has received support has received support for contracts Juan Rodes (JR16/00024) and from Fondo de Investigación en Salud (PI17/02162 and PI22/01589) from Instituto de Salud Carlos III, Spain, and has engaged in consulting and/or participated as speaker in events organized by Roche, Novartis, Merck, and Sanofi. Cristina Auger has nothing to disclose. Jaume Sastre-Garriga serves as co-Editor for Europe for the Multiple Sclerosis Journal and as Editor-in-Chief of Revista de Neurología, receives research support from Fondo de Investigaciones Sanitarias (19/950 and 22/750) and in the last 12 months has served as a consultant/speaker for BMS, Roche, Sanofi, Janssen, and Merck., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Treponema pallidum can invade the central nervous system (CNS) early in its infection, causing neurosyphilis. Neurosyphilis typically presents with meningovasculitis in the acute or subacute phase, while tabes dorsalis and dementia paralytica are classical conditions in the later stages. However, syphilis is often misdiagnosed as other conditions such as tumors or autoimmune diseases including vasculitis and encephalitis, which is why the condition is known as "The Great Mimicker." The increasing incidence of syphilis in recent years emphasizes the importance of early diagnosis and treatment; however, its multiple clinical manifestations impose diagnostic challenges for clinicians because it resembles other diseases. In this case series, we present the impressive manifestations of neurosyphilis through three unique radiological presentations., Case Presentation: Case 1 details optic nerve involvement in an HIV-positive male, where MRI and fundoscopic findings confirmed syphilitic optic neuritis. Case 2 describes a patient in her pregnancy initially suspected of acoustic neuroma on MRI, later diagnosed with syphilitic gumma affecting the inner ear canal. Case 3 is a young male with clinical features mimicking temporal arteritis, ultimately identified as skull osteomyelitis secondarily causing inflammation of the musculus temporalis and meningitis., Conclusions: These cases underscore the necessity of considering syphilis in differential diagnoses, given the diversity of its clinical presentations. Radiology plays an important role in avoiding unnecessary interventions. The increasing prevalence of recurrent syphilis imposes diagnostic challenges, emphasizing the importance of the early diagnosis and treatment of neurosyphilis by clinicians., (© 2024. The Author(s).)

Background: Optic neuritis, myelitis, and neuromyelitis optica spectrum disorder (NMOSD) have been associated with antibodies against myelin oligodendrocyte glycoprotein-immunoglobulin G (anti-MOG-IgG). Furthermore, patients with radiological and demographic features atypical for multiple sclerosis (MS) with optic neuritis and myelitis also demonstrate antibodies against aquaporin-4 and anti-MOG-IgG. However, data on the diagnosis, treatment, follow-up, and prognosis in patients with anti-MOG-IgG are limited., Aims: To evaluate the clinical, radiological, and demographic characteristics of patients with anti-MOG-IgG., Study Design: Multicenter, retrospective, observational study., Methods: Patients with blood samples demonstrating anti-MOG-IgG that had been evaluated at the Neuroimmunology laboratory at Ondokuz Mayıs University’s Faculty of Medicine were included in the study., Results: Of the 104 patients with anti-MOG-IgG, 56.7% were women and 43.3% were men. Approximately 2.4% of the patients were diagnosed with MS, 15.8% with acute disseminated encephalomyelitis (ADEM), 39.4% with NMOSD, 31.3% with isolated optic neuritis, and 11.1% with isolated myelitis. Approximately 53.1% of patients with spinal involvement at clinical onset demonstrated a clinical course of NMOSD. Thereafter, 8.8% of these patients demonstrated a clinical course similar to MS and ADEM, and 28.1% demonstrated a clinical course of isolated myelitis. The response to acute attack treatment was lower and the disability was higher in patients aged > 40 years than patients aged < 40 years at clinical onset. Oligoclonal band was detected in 15.5% of the patients., Conclusion: For patients with NMOSD and without anti-NMO antibodies, the diagnosis is supported by the presence of anti-MOG-IgG. Furthermore, advanced age at clinical onset, Expanded Disability Status Scale (EDSS) score at clinical onset, spinal cord involvement, and number of attacks may be negative prognostic factors in patients with anti-MOG-IgG.

Introduction: Recent diagnostic criteria for optic neuritis include T2-hyperintensity of the optic nerve (ON), even without associated contrast enhancement. However, isolated ON-T2-hyperintensity is a nonspecific finding found in any optic neuropathy or severe retinopathy. We applied the 2022 optic neuritis diagnostic criteria to a cohort of patients with noninflammatory optic neuropathy and ON-T2-hyperintensity in at least one eye, to assess the rate of optic neuritis misdiagnosis using these criteria., Methods: Retrospective study of consecutive patients who underwent brain/orbit MRI with/without contrast between 07/01/2019 and 06/30/2022. Patients with ON-T2-hyperintensity in at least one eye were included. The 2022 optic neuritis diagnostic criteria were applied to patients with noninflammatory optic neuropathies who had an ophthalmologic examination available for review., Results: Of 150 patients included, 85/150 had compressive optic neuropathy; 32/150 had glaucoma; 12/150 had papilledema; 8/150 had hereditary (3), radiation-induced (3), nutritional (1), traumatic (1) optic neuropathies (none fulfilled the criteria); 13/150 had ischemic optic neuropathy and 4 fulfilled the criteria as definite optic neuritis due to contrast enhancement of the ON head. Seven additional patients would have satisfied the diagnostic criteria if red flags for alternative diagnoses had been overlooked., Discussion: The application of the 2022 optic neuritis diagnostic criteria in patients with noninflammatory optic neuropathy and ON-T2-hyperintensity in at least one ON resulted in misdiagnosis of optic neuritis in only 4 patients because of ON head enhancement, all with nonarteritic anterior ischemic optic neuropathy. Neuro-ophthalmologic evaluation and exclusion of the ON head as a location in the MRI criteria would have prevented optic neuritis misdiagnosis in our study., (© 2024. Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: To analyze the risk factors that affect the prognosis of patients with optic neuritis through imaging examinations and clinical data analysis., Methods: 130 patients with optic neuritis admitted to our hospital from February 2018 to February 2022 were selected as the study subjects. They were divided into a poor prognosis group (n = 52) and a good prognosis group (n = 78) based on their prognosis. Imaging examination and clinical data analysis, along with the assessment of the predictive value of statistically significant continuous variables using ROC experiments and risk factors using logistic regression were performed., Results: The results showed that there was no statistically significant difference in general data such as gender and BMI between the two groups (P > .05). Compared with the group with good prognosis, the group with poor prognosis had higher age (34.47 ± 1.58 years vs 35.81 ± 2.60 years), onset to visit interval (1.81 ± 0.40 weeks vs 2.50 ± 0.64 weeks), VCAM-1 (608.70 ± 42.80 ng/mL vs 625.58 ± 35.62 ng/mL), recurrence rate (48.72% vs 69.23%), optic nerve atrophy rate (3.85% vs 15.38%), eye rotation pain rate (28.21% vs 30.77%), and MRI long T2 signal rate (21.79% vs 40.38%). The proportion of MRI T1 enhanced signals was relatively high (17.95% vs 34.62%) (P < .05). Age, the interval between onset and visit time, and AUC of VCAM-1 were 0.657, 0.785, and 0.621, and the optimal cutoff values were 35 years old, 2 weeks old, and 620.29 ng/mL; 95% CI was (0.596 0.738), (0.704 0.852), and (0.532 0.704), P < .05., Conclusion: Age (>35 years old), recurrence (yes), interval between onset and visit (>2 weeks), MRI long T2 signal (yes), and MRI T1 enhanced signal (yes) are all risk factors that affect the prognosis of patients with optic neuritis. Clinical attention should be paid to high-risk populations.

Purpose: Despite mounting evidence indicating that aquaporin-4 antibody-positive optic neuritis (AQP4-ON) presents a less favorable prognosis than other types of optic neuritis, there exists substantial heterogeneity in the prognostic outcomes within the AQP4-ON cohort. Considering the persistent debate over the role of MRI in assessing the prognosis of optic neuritis, we aim to investigate the correlation between the MRI appearance and long-term visual prognosis in AQP4-ON patients., Methods: We retrospectively reviewed the ophthalmological and imaging data of AQP4-ON patients admitted to our Neuro-ophthalmology Department from January 2015 to March 2018, with consecutive follow-up visits for a minimum of 3 years., Results: A total of 51 AQP4-ON patients (59 eyes) meeting the criteria were enrolled in this research. After assessing the initial orbital MR images of each patient at the first onset, we observed the involvement of the canalicular segment (p < 0.001), intracranial segment (p = 0.004), optic chiasm (p = 0.009), and the presence of LEON (p = 0.002) were significantly different between recovery group and impairment group. For quantitative measurement, the length of the lesions is significantly higher in the impairment group (20.1 ± 9.3 mm) than in the recovery group (12.5 ± 5.3 mm) (p = 0.001)., Conclusion: AQP4-ON patients with involvement of canalicular, intracranial segment and optic chiasm of the optic nerve, and the longer range of lesions threaten worse vision prognoses. Timely MR examination during the initial acute phase can not only exclude the intracranial or orbital mass lesions but also indicate visual prognosis in the long term., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Alterations of the superficial retinal vasculature are commonly observed in multiple sclerosis (MS) and can be visualized through optical coherence tomography angiography (OCTA)., Objectives: This study aimed to examine changes in the retinal vasculature during MS and to integrate findings into current concepts of the underlying pathology., Methods: In this cross-sectional study, including 259 relapsing-remitting MS patients and 78 healthy controls, we analyzed OCTAs using deep-learning-based segmentation algorithm tools., Results: We identified a loss of small-sized vessels (diameter < 10 µm) in the superficial vascular complex in all MS eyes, irrespective of their optic neuritis (ON) history. This alteration was associated with MS disease burden and appears independent of retinal ganglion cell loss. In contrast, an observed reduction of medium-sized vessels (diameter 10-20 µm) was specific to eyes with a history of ON and was closely linked to ganglion cell atrophy., Conclusion: These findings suggest distinct atrophy patterns in retinal vessels in patients with MS. Further studies are necessary to investigate retinal vessel alterations and their underlying pathology in MS., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: R.W. received a poster grant by Novartis. L.A. received a research grant by Novartis and travel grants by Novartis, Sanofi and Horizon therapeutics. B.H. has served on scientific advisory boards for Novartis; he has served as DMSC member for AllergyCare, Sandoz, Polpharma, Biocon and TG therapeutics; he or his institution have received speaker honoraria from Desitin; his institution received research grants from Regeneron and Roche for MS research. He holds part of two patents; one for the detection of antibodies against KIR4.1 in a subpopulation of patients with MS and one for genetic determinants of neutralizing antibodies to interferon. All conflicts are not relevant to the topic of the study. B.K. received travel support and speaking honoraria from Novartis Deutschland GmbH, Teva Deutschland, Merck, and Heidelberg Engineering and served at the advisory board of Merck. He received a research grant from Novartis. L.K., A.W., D.R., T.K. and M.J.M. have nothing to disclose.

Background: Aneurysmal bone cyst (ABC) is an uncommon, benign, vascular multicystic bony lesion that most frequently develops in the first two decades of life. The metaphysis of long bones, pelvic, and vertebral column are the most common locations. The precise underlying pathophysiology of ABCs formation remains unclear; however, it is believed that reactive processes subsequent to trauma or vascular disturbance may play an important role. Involvement of the skull base rarely occurs with a prevalence of up to 5% of intracranial ABCs., Case Presentations: An 18-year-old adolescent female with a history of progressive blurred vision since three months ago presented to our office. The brain and orbital MRI demonstrated no abnormal findings. After three months of glucocorticoid treatment with the diagnosis of multiple sclerosis, the visual impairment of the left eye deteriorated abruptly. The patient underwent an MRI and the imaging study demonstrated a well-defined 30 × 22 × 20-mm lesion at the anterior clinoid process with an extension to the optic canal and ethmoid sinus. The patient underwent pterional craniotomy, and the tumor was resected. The histopathological examination was suggestive of ABC., Conclusion: ABC and other conditions should be considered in young-age people with an early unilateral decline in vision and imaging studies should be obtained in early stages and during follow-ups., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Leber's hereditary optic atrophy (LHON) is a genetic optic neuropathy that is more prevalent in young males but can occur from childhood to old age. The primary cause is mitochondrial genetic mutations, which are associated with dysfunction of mitochondrial electron transport chain complex I. It manifests as acute to subacute visual impairment, often starting unilaterally but progressing to involve both eyes within weeks to months. Visual loss is severe, with many patients having corrected visual acuity below 0.1. The differential diagnosis of optic neuritis is essential, and assessments such as pupillary light reflex, fluorescein fundus angiography, and magnetic resonance imaging can be useful for differentiation. LHON should be considered as one of the differential diagnoses for optic neuritis, and collaboration between neurologists and ophthalmologists is crucial for accurate diagnosis and appropriate treatment.

Purpose: We aimed to determine the feasibility of using DKI to characterize pathological changes in nonarteritic anterior ischemic optic neuropathy (NAION) and to differentiate it from acute optic neuritis (ON)., Methods: Orbital DKI was performed with a 3.0 T scanner on 75 patients (51 with NAION and 24 with acute ON) and 15 healthy controls. NAION patients were further divided into early and late groups. The mean kurtosis (MK), axial kurtosis (AK), radial kurtosis (RK), mean diffusivity (MD), fractional anisotropy (FA), radial diffusivity (RD), and axial diffusivity (AD) were calculated to perform quantitative analyses among groups; and receiver operating characteristic curve analyses were also performed to determine their effectiveness of differential diagnosis. In addition, correlation coefficients were calculated to explore the correlations of the DKI-derived data with duration of disease., Results: The MK, RK, and AK in the affected nerves with NAION were significantly higher than those in the controls, while the trend of FA, RD, and AD was a decline; in acute ON patients, except for RD, which increased, all DKI-derived kurtosis and diffusion parameters were significantly lower than controls (all P < 0.008). Only AK and MD had statistical differences between the early and late groups. Except for MD (early group) and FA, all other DKI-derived parameters were higher in NAION than in acute ON; and parameters in the early group showed better diagnostic efficacy in differentiating NAION from acute ON. Correlation analysis showed that time was negatively correlated with MK, RK, AK, and FA and positively correlated with MD, RD, and AD (all P < 0.05)., Conclusion: DKI is helpful for assessing the specific pathologic abnormalities resulting from ischemia in NAION by comparison with acute ON. Early DKI should be performed to aid in the diagnosis and evaluation of NAION., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: To explore associations of the main component (P100) of visual evoked potentials (VEP) to pre- and postchiasmatic damage in multiple sclerosis (MS)., Methods: 31 patients (median EDSS: 2.5), 13 with previous optic neuritis (ON), and 31 healthy controls had VEP, optical coherence tomography and magnetic resonance imaging. We tested associations of P100-latency to the peripapillary retinal nerve fiber layer (pRNFL), ganglion cell/inner plexiform layers (GCIPL), lateral geniculate nucleus volume (LGN), white matter lesions of the optic radiations (OR-WML), fractional anisotropy of non-lesional optic radiations (NAOR-FA), and to the mean thickness of primary visual cortex (V1). Effect sizes are given as marginal R 2 (mR 2 )., Results: P100-latency, pRNFL, GCIPL and LGN in patients differed from controls. Within patients, P100-latency was significantly associated with GCIPL (mR 2  = 0.26), and less strongly with OR-WML (mR 2  = 0.17), NAOR-FA (mR 2  = 0.13) and pRNFL (mR 2  = 0.08). In multivariate analysis, GCIPL and NAOR-FA remained significantly associated with P100-latency (mR 2  = 0.41). In ON-patients, P100-latency was significantly associated with LGN volume (mR 2  = -0.56)., Conclusions: P100-latency is affected by anterior and posterior visual pathway damage. In ON-patients, damage at the synapse-level (LGN) may additionally contribute to latency delay., Significance: Our findings corroborate post-chiasmatic contributions to the VEP-signal, which may relate to distinct pathophysiological mechanisms in MS., (Copyright © 2024 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)

Background: Myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease (MOGAD) exhibits phenotypic diversity and it varies by age. However, less is known about whether the manifestations of isolated MOG antibody-associated optic neuritis (iMOG-ON) vary across different age groups. We aimed to investigate the clinical and prognostic features of iMOG-ON in young and middle-aged adult patients., Methods: Patients with iMOG-ON were enrolled in the Department of Neurology, Beijing Tongren Hospital, Capital Medical University between January 2018 and October 2021. Medical records were reviewed to obtain clinical data and orbital MRI images of adult patients with iMOG-ON. Multivariate linear regression analysis was performed to investigate the associations between final best-corrected visual acuity (BCVA) in logMAR and clinical characteristics., Results: Based on the age of onset, 70 patients were divided into 2 groups: 38 young (< 46 years; female/male = 0.76:1) and 32 middle-aged (≥ 46 years; female/male = 5.56:1) adults. There were statistical differences in both the female-to-male ratio and frequencies of contrast enhancement of the optic nerve sheaths and surrounding orbital tissues between both groups (p = 0.001, p = 0.004, respectively). The average follow-up periods were 28.04 ± 11.22 months. The median final BCVA was 0 (0 - 0.50) logMAR and 0.5 (0.3 - 1.0) logMAR in the young and middle-aged patients, respectively (p = 0.000). The multivariate linear regression analysis indicated significant positive relationships between final BCVA and age of onset (p = 0.038, 95 % CI: 0.020 - 0.728), sex (p = 0.030, 95 % CI: -0.793 - -0.042), BCVA at nadir (p = 0.000, 95 % CI: 0.164 - 0.386), and numbers of segments of optic nerve lesions (p = 0.009, 95 % CI: 0.068 - 0.450) with a coefficient of determination (R 2 ) of 0.359 after adjusting for prior attacks of ON, time intervals between sudden-onset vision loss and administration of intravenous methylprednisolone, and corticosteroid dosages. The worst final BCVA was observed in afflicted eyes with lesions extending across three segments of the optic nerve., Conclusion: Compared to young adults with iMOG-ON, the middle-aged patients tended to have a female predominance, higher frequencies of perineural enhancement, and worse visual outcomes. In addition to age of onset, visual recovery may also be influenced by patient's sex, BCVA at nadir, and lengths of longitudinally expansive lesions of the optic nerve to a certain extent., Competing Interests: Declaration of competing interest All authors declared no conflict of interest., (Copyright © 2024. Published by Elsevier B.V.)

Background: Optic neuritis (ON) is a common feature of inflammatory demyelinating diseases (IDDs) such as multiple sclerosis (MS), aquaporin 4-antibody neuromyelitis optica spectrum disorder (AQP4 + NMOSD) and myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD). However, the involvement of the optic chiasm (OC) in IDD has not been fully investigated., Aims: To examine OC differences in non-acute IDD patients with (ON+) and without ON (ON-) using magnetisation transfer ratio (MTR), to compare differences between MS, AQP4 + NMOSD and MOGAD and understand their associations with other neuro-ophthalmological markers., Methods: Twenty-eight relapsing-remitting multiple sclerosis (RRMS), 24 AQP4 + NMOSD, 28 MOGAD patients and 32 healthy controls (HCs) underwent clinical evaluation, MRI and optical coherence tomography (OCT) scan. Multivariable linear regression models were applied., Results: ON + IDD patients showed lower OC MTR than HCs (28.87 ± 4.58 vs 31.65 ± 4.93; p = 0.004). When compared with HCs, lower OC MTR was found in ON + AQP4 + NMOSD (28.55 ± 4.18 vs 31.65 ± 4.93; p = 0.020) and MOGAD (28.73 ± 4.99 vs 31.65 ± 4.93; p = 0.007) and in ON- AQP4 + NMOSD (28.37 ± 7.27 vs 31.65 ± 4.93; p = 0.035). ON+ RRMS had lower MTR than ON- RRMS (28.87 ± 4.58 vs 30.99 ± 4.76; p = 0.038). Lower OC MTR was associated with higher number of ON (regression coefficient (RC) = -1.15, 95% confidence interval (CI) = -1.819 to -0.490, p = 0.001), worse visual acuity (RC = -0.026, 95% CI = -0.041 to -0.011, p = 0.001) and lower peripapillary retinal nerve fibre layer (pRNFL) thickness (RC = 1.129, 95% CI = 0.199 to 2.059, p = 0.018) when considering the whole IDD group., Conclusion: OC microstructural damage indicates prior ON in IDD and is linked to reduced vision and thinner pRNFL., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship and/or publication of this article: AB has received a research grant from the Italian Society of Neurology; she has been awarded a MAGNIMS-ECTRIMS fellowship in 2023. RC received speaker honoraria/travel support from Roche, Merck Serono, UCB, Sanofi-Genzyme, Novartis, and Janssen, and received a research grant from the Italian Ministry of University and Research. FP received a Guarantors of Brain fellowship 2017-2020. CT is currently being funded by a Miguel Servet contract, awarded by the Instituto de Salud Carlos III (ISCIII), Ministerio de Ciencia e Innovación de España (CP23/00117). She has also received a 2020 Junior Leader La Caixa Fellowship (fellowship code: LCF/BQ/PI20/11760008), awarded by “la Caixa” Foundation (ID 100010434), a 2021 Merck’s Award for the Investigation in MS, awarded by Fundación Merck Salud (Spain), a 2021 Research Grant (PI21/01860) awarded by the ISCIII, Ministerio de Ciencia e Innovación de España, and a FORTALECE research grant (FORT23/00034) also by the ISCIII, Ministerio de Ciencia e Innovación de España. In 2015, she received an ECTRIMS Post-doctoral Research Fellowship and has received funding from the UK MS Society. She is a member of the Editorial Board of Neurology Journal and Multiple Sclerosis Journal. She has also received honoraria from Roche, Novartis, Merck, Immunic Therapeutics, and Bristol Myers Squibb. She is a steering committee member of the O’HAND trial and of the Consensus group on Follow-on DMTs. BK is supported by the NIHR BRC at UCL. FDA has received congress fees or speaker honoraria and/or acted as a consultant for Neurology Academy, Coloplast, Janssen, Merck, Novartis, Roche,Sanofi. WJB has received speaker honoraria and/or acted as a consultant for Biogen, Janssen, Merck, Neuraxpharm, Novartis, Roche, Sanofi, Sandoz and Viatris; he is supported by the NIHR UCLH Biomedical Research Centre. FB is Steering committee or Data Safety Monitoring Board member for Biogen, Merck, ATRI/ACTC and Prothena. He is consultant for Roche, Celltrion, Rewind Therapeutics, Merck, IXICO, Jansen, Combinostics. He has research agreements with Merck, Biogen, GE Healthcare, Roche. Co-founder and shareholder of Queen Square Analytics LTD. OC is a member of independent DSMB for Novartis, gave a teaching talk on McDonald criteria in a Merck local symposium, and contributed to an Advisory Board for Biogen; she is Deputy Editor of Neurology, for which she receives an honorarium. Merck. AD, VC, DW, JS, MCY, and RN have no disclosure. ATT has speaker honoraria from Merck, Biomedia, Sereno Symposia International Foundation, Bayer and At the Limits and meeting expenses from Merck, Biogen Idec and Novartis. Supported by recent grants from the MRC (MR/S026088/1), NIHR BRC (541/CAP/OC/818837) and RoseTrees Trust (A1332 and PGL21/10079). Associate editor for Frontiers in Neurology – Neuro-ophthalmology section and on the editorial board for Neurology and Multiple Sclerosis Journal.

Background and Objectives: We aimed to assess the presence of retinal neurodegeneration independent of optic neuritis (ON) in myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) and to investigate the development of trans-synaptic anterograde degeneration in these patients after ON., Methods: Cross-sectional, retrospective study of 34 adult patients with MOGAD and 23 healthy controls (HC). Clinical, optical coherence tomography (OCT), and MRI data were collected. Peripapillary retinal nerve fiber layer (pRNFL) and ganglion cell inner plexiform layer (GCIPL) were obtained using Heidelberg Spectralis. FreeSurfer7 was used to obtain the lateral geniculate nucleus (LGN), occipital volume fractions (to total estimated intracranial volume), and occipital cortical thickness. For the anterior visual pathway, the analysis was conducted using eyes, classified based on the history of ON (Eye-ON and Eye-NON) and compared with Eye-HC. The analysis of OCT and brain volumetric measures was conducted comparing MOGAD-ON, MOGAD-NON, and HC groups. The analysis of covariance with a Bonferroni-adjusted post hoc test was used to test differences between groups and linear regression analysis to evaluate OCT/MRI associations; age and sex were considered as covariates., Results: 24 (70.5%) patients had a prior ON. Median pRNFL and GCIPL thickness (um) was significantly reduced in Eye-ON vs EyeNON and HC (pRNFL: 69.4 (17.3), 89.6 (13.7), 98.2 (11.7), p < 0.001; GCIPL: 55.8 (8.7), 67.39 (8.7), 72.6 (4.5), p < 0.001). pRNFL and GCIPL thickness had a negative correlation with the number of ON episodes ( p = 0.025 and p = 0.031, respectively). LGN volume fraction was significantly lower in patients with MOGAD-ON than in HC (0.33 (0.05) vs 0.39 (0.04), p = 0.002). The occipital cortical thickness was lower in MOGAD-ON compared with MOGAD-NON and HC ( p = 0.010). In patients with MOGAD-ON, pRNFL correlated with LGN volume ( p = 0.006), occipital thickness ( p = 0.002), and the medial occipital cortex ( p = 0.002), but not the lateral occipital lobe., Discussion: Compared with HC, MOGAD-ON exhibits reduced retinal thickness, primarily influenced by the presence and the number of prior ON episodes. Moreover, MOGAD-ON demonstrates significant atrophy in the retinal, subcortical, and cortical regions of the visual pathway, distinguishing them from MOGAD-NON and HC. These findings suggest that in patients with MOGAD neurodegeneration is tightly correlated with damage to the involved pathway.

Objectives: Optic nerve head edema (ONHE) detected by fundoscopy is observed in one-third of patients presenting optic neuritis (ON). While ONHE is an important semiological feature, the correlation between ONHE and optic nerve head MRI abnormalities (ONHMA), sometimes called "optic nerve head swelling," remains unknown. Our study aimed to assess the diagnostic accuracy of T2 fluid-attenuated inversion recovery (FLAIR) MRI sequence in detecting ONHE in patients with acute ON., Methods: In the present single-center study, data were extracted from two prospective cohort studies that consecutively included adults with a first episode of acute ON treated between 2015 and 2020. Two experienced readers blinded to study data independently analyzed imaging. A senior neuroradiologist resolved any discrepancies. The primary judgment criterion of ONHMA was assessed as optic nerve head high signal intensity on gadolinium-enhanced T2FLAIR MRI sequence. Its diagnostic accuracy was evaluated with both the gold standard of ONHE on fundus photography (FP) and peripapillary retinal nerve fiber layer thickening on optic coherence tomography (OCT)., Results: A total of 102 patients were included, providing 110 affected and 94 unaffected optic nerves. Agreement was high between the different modalities: 92% between MRI and FP (k = 0.77, 95% CI: 0.67-0.88) and 93% between MRI and OCT (k = 0.77, 95% CI: 0.67-0.87). MRI sensitivity was 0.84 (95% CI: 0.70-0.93) and specificity was 0.94 (95% CI: 0.89-0.97) when compared with the FP., Conclusion: Optic nerve head high T2FLAIR signal intensity corresponds indeed to the optic nerve head edema diagnosed by the ophthalmologists. MRI is a sensitive tool for detecting ONHE in patients presenting acute ON., Clinical Relevance Statement: In patients with optic neuritis the high T2FLAIR (fluid-attenuated inversion recovery) signal intensity of the optic nerve head corresponds indeed to optic nerve head edema, which is a useful feature in optic neuritis etiological evaluation and treatment., Key Points: Optic nerve head edema is a prominent clinical feature of acute optic neuritis and is usually diagnosed during dilated or non-dilated eye fundus examination. Agreement was high between magnetic resonance imaging, fundus photography, and optical coherence tomography. Optic nerve head high T2 fluid attenuation inversion recovery signal intensity is a promising detection tool for optic nerve head edema in patients presenting acute optic neuritis., (© 2023. The Author(s), under exclusive licence to European Society of Radiology.)

Purpose: To investigate the rate of development of symptomatic central nervous system (CNS) demyelinating attacks or recurrent optic neuritis (ON) after the first episode of ON and its risk factors for Korean pediatric patients., Methods: This multicenter retrospective cohort study included the patients under 18 years of age (n=132) diagnosed with ON without previous or simultaneous CNS demyelinating diseases. We obtained the clinical data including the results of neuro-ophthalmological examinations, magnetic resonance images (MRIs), antibody assays, and laboratory tests. We investigated the chronological course of demyelinating disease with respect to the occurrence of neurological symptoms and/or signs, and calculated the 5-year cumulative probability of CNS demyelinating disease or ON recurrence.  RESULTS: During the follow-up period (63.1±46.7 months), 18 patients had experienced other CNS demyelinating attacks, and the 5-year cumulative probability was 14.0±3.6%. Involvement of the extraorbital optic nerve or optic chiasm and asymptomatic lesions on the brain or spinal MRI at initial presentation were significant predictors for CNS demyelinating attack after the first ON. The 5-year cumulative probability of CNS demyelinating attack was 44.4 ± 24.8% in the AQP4-IgG group, 26.2±11.4% in the MOG-IgG group, and 8.7±5.9% in the double-negative group (P=0.416). Thirty-two patients had experienced a recurrence of ON, and the 5-year cumulative probability was 24.6±4.0%. In the AQP4-IgG group, the 5-year cumulative probability was 83.3±15.2%, which was significantly higher than in the other groups (P<0.001)., Conclusions: A careful and multidisciplinary approach including brain/spinal imaging and antibody assay can help predict further demyelinating attacks in pediatric ON patients., (© 2023. Fondazione Società Italiana di Neurologia.)

Purpose: The optic chiasm (OC) is a central structure in the visual pathway and can be visualized in conventional MRI, but no consensus regarding its measurement has been defined. We aim to investigate the most reproducible manual approach to OC measurement and to explore associations of OC with optical coherence tomography (OCT) parameters, and automatic brain segmentation (FreeSurfer) in subacute optic neuritis (sON), multiple sclerosis without optic neuritis (MSwoON), and healthy subjects (HS)., Materials and Methods: We reproduced two previously reported methodologies and implemented a new proposed simplified approach, entitled optic chiasm mean area (OCMA). The intra and inter-rater reliability and reproducibility were assessed through the intraclass correlation (ICC) and Dice similarity (DSC) coefficients. Partial correlations were calculated to gauge the associations between OCMA fraction (OCMA divided by total intracranial volume), brain regional segmentations derived from FreeSurfer, and OCT parameters., Results: We have analysed 43 sON, 20 MSwoON, and 20 HS. OCMA presented better results for reliability in both intra- and inter-rater analysis (excellent ICC and DSC with over 80% overlap between masks), as compared to the other two approaches. OCMA fraction was associated with OC volume fraction obtained with Freesurfer in all groups, brain parenchymal fraction, and OCT parameters in MSwoON., Conclusions: The OCMA is a simplified approach to measure OC atrophy, has a higher reliability than the current approaches and shows association with an automated method. OC-derived measures seem to reflect diffuse neurodegenerative damage, whereas, in patients with subacute ON, it may be associated with local damage., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: NB: has received a Fellowship grant from the European Committee for Treatment and Research in Multiple Sclerosis. DP: has received a research grant from Biogen Idec and a from Fondo de Investigación Sanitaria (PI18/00823, PI22/01709), co-funded by the European Union. NM-O: has a predoctoral grant Rio Hortega, from the Instituto de Salud Carlos III (CM21/00018). BR - A: has received speaking honoraria from Merck and honoraria for consulting services from Novartis. CA: has nothing to disclose. MA: has nothing to disclose. SC: has nothing to disclose. AV-J: has received support for contracts Juan Rodes (JR16/00024) and from Fondo de Investigación en Salud (PI17/02162 and PI22/01589) from Instituto de Salud Carlos III, Spain, and has engaged in consulting and/or participated as a speaker in events organized by Roche, Novartis, Merck, and Sanofi. MT: has received compensation for consulting services, speaking honoraria, and research support from Almirall, Bayer Schering Pharma, Biogen-Idec, Genzyme, Janssen, Merck-Serono, Novartis, Roche, Sanofi-Aventis, Viela Bio, and Teva Pharmaceuticals. XM: has received speaking honoraria and travel expenses for participation in scientific meetings, has been a steering committee member of clinical trials or participated in advisory boards of clinical trials in the past years with Abbvie, Actelion, Alexion, Biogen, Bristol-Myers Squibb/Celgene, EMD Serono, Genzyme, Hoffmann-La Roche, Immunic, Janssen Pharmaceuticals, Medday, Merck, Mylan, Nervgen, Novartis, Sandoz, Sanofi-Genzyme, Teva Pharmaceutical, TG Therapeutics, Excemed, MSIF, and NMSS”. AR: serves/ed on scientific advisory boards for Novartis, Sanofi-Genzyme, SyntheticMR, TensorMedical, Roche, Biogen, and OLEA Medical, and has received speaker honoraria from Bayer, Sanofi-Genzyme, Merck-Serono, Teva Pharmaceutical Industries Ltd, Novartis, Roche, Bristol-Myers, and Biogen. JS-G: serves as co-editor for Europe for the Multiple Sclerosis Journal and as Editor-in-Chief of Revista de Neurología, receives research support from Fondo de Investigaciones Sanitarias (19/950 and 22/750) and has served as a consultant/speaker for Biogen, Celgene/Bristol Meyers Squibb, Sanofi, Novartis, and Merck., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background and Purpose: Myelin oligodendrocyte glycoprotein-antibody associated disease (MOGAD) is an increasingly recognized cause of demyelinating disease in children. The purpose of this study is to characterize the CNS imaging manifestations of pediatric MOGAD and identify clinical and imaging variables associated with relapse., Materials and Methods: We retrospectively identified children with serum antibody-positive MOGAD evaluated at our institution between 1997 and 2020. Clinical and demographic data were collected. MRIs of the brain, orbit, and spine at presentation and relapse were reviewed for location and pattern of abnormality., Results: Among 61 cases (34 girls), mean age at presentation was 7 years (IQR 4-11). At presentation, there was imaging involvement of the brain in 78.6% (44/56), optic pathway in 55.4% (31/56), and spine in 19.6% (11/56). Brain involvement was commonly in the frontal (70.5%, 31/44) and subcortical (75%, 33/44) white matter, with involvement of the thalamus and pons in 47.7% each (21/44). Optic neuritis (ON) was commonly bilateral (80.6%, 25/31) involving intraorbital segments (77.4%, 24/31). Spinal cord lesions were typically cervical (72.7%, 8/11) and multifocal (72.7%, 8/11).The imaging patterns were age-dependent; children ≤9 years more commonly demonstrated ADEM-like imaging pattern at presentation (39.4%, 13/33) and first relapse (8/23, 34.8%), while children >9 years more commonly had ON at presentation (34.8%, 8/23, P  = .001) and FLAIR-hyperintense lesions in anti-MOG-associated encephalitis with seizures at first relapse (5/18, 27.8%, P  = .008)., Conclusions: We describe the CNS imaging findings in pediatric MOGAD. The imaging pattern is age-dependent at presentation and first relapse. Younger age at presentation is associated with longer time to relapse., (© 2024 by American Journal of Neuroradiology.)

Purpose: To compare superficial and deep vascular characteristics of the optic disc in retrobulbar optic neuritis using optical coherence tomography angiography (OCT-A)., Methods: Nineteen patients with unilateral non-infectious retrobulbar neuritis were included in the study. The contralateral eyes of each patient were served as controls. OCT-A scans of the optic discs were performed in a 4.5 × 4.5 mm rectangular area, while macular OCT-A scans were performed in a 6 × 6 mm rectangular area. Various parameters, including radial peripapillary capillary (RPC) density, peripapillary retinal nerve fibre layer (pRNFL) thickness, cup volume, rim area, disc area, cup-to-disc (c/d) area ratio, and vertical and horizontal c/d ratios were automatically obtained using the instrument software. The density for superficial capillary plexus (SCP) and deep capillary plexus (DCP) were assessed using macular OCT-A. Parapapillary choroidal microvascular (PPCMv) density was calculated using MATLAB software., Results: Parafoveal inferior, perifoveal total and inferior SCP densities were significantly decreased in eyes with optic neuritis when compared with contralateral control eyes in OCT-A measurements (respectively, p = 0.027, p = 0.041, p = 0.045). The axial lengths, (p = 0.72), vertical and horizontal cup-disc ratios, and disc area, cup-disc areas, cup volumes, and pRNFL thicknesses between the groups were similar (for each, p>0.05)., Conclusions: This study demonstrated for the first time that patients with retrobulbar optic neuritis had decreased SCP densities, though it did not cause any changes in PPCMv density., Competing Interests: Declaration of Competing Interest No potential conflict of interest was reported by the authors., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Current diagnostic criteria for multiple sclerosis (MS) do not consider the optic nerve as a typical topography for establishing the diagnosis. Recent studies have proved the utility of optic nerve magnetic resonance imaging, optical coherence tomography and visual evoked potentials in detecting optic nerve lesions during the early stages of MS. In addition, emerging evidence supports the inclusion of optic nerve topography as a fifth region to fulfil the dissemination in space criteria. Anticipating a modification in the McDonald criteria, it is crucial for neurologists to familiarize with the diagnostic properties of each test in detecting optic nerve lesions and understand how to incorporate them into the MS diagnostic process. Therefore, the objective of this article is to review the existing evidence supporting the use of these tests in the diagnostic process of MS and provide a practical algorithm that can serve as a valuable guide for clinical practice., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship and/or publication of this article: A.V.-J. has received support for contracts Juan Rodes (JR16/00024) and from Fondo de Investigación en Salud (PI17/02162 and PI22/01589) from Instituto de Salud Carlos III, Spain, and has engaged in consulting and/or participated as speaker in events organized by Roche, Novartis, Merck and Sanofi. J.S.-G. serves as co-editor for Europe for the Multiple Sclerosis Journal and as Editor-in-Chief of Revista de Neurología, receives research support from Fondo de Investigaciones Sanitarias (19/950 and 22/750) and in the past 12 months has served as a consultant/speaker for BMS, Roche, Sanofi, Janssen and Merck. M.T. has received compensation for consulting services, speaking honoraria and research support from Almirall, Bayer Schering Pharma, Biogen-Idec, Genzyme, Janssen, Merck-Serono, Novartis, Roche, Sanofi-Aventis, Viela Bio and Teva Pharmaceuticals. Data Safety Monitoring Board for Parexel and UCB Biopharma. A.R. served on scientific advisory boards for Novartis, Sanofi-Genzyme, Synthetic MR, TensorMedical, Roche and Biogen, and has received speaker honoraria from Bayer, Sanofi-Genzyme, Merck-Serono, Teva Pharmaceutical Industries Ltd, Novartis, Roche, Bristol-Myers and Biogen, is CMO and co-founder of TensorMedical, and receives research support from Fondo de Investigación en Salud (PI19/00950 and PI22/01589) from Instituto de Salud Carlos III, Spain. X.M. has received speaking honoraria and travel expenses for participation in scientific meetings, has been a steering committee member of clinical trials or participated in advisory boards of clinical trials in the past years with Abbvie, Actelion, Alexion, Biogen, Bristol-Myers Squibb/Celgene, EMD Serono, Genzyme, Hoffmann-La Roche, Immunic, Janssen Pharmaceuticals, Medday, Merck, Mylan, Nervgen, Novartis, Sandoz, Sanofi-Genzyme, Teva Pharmaceutical, TG Therapeutics, Excemed, MSIF and NMSS.

Background and Objectives: The optic nerve is not one of the areas of the CNS that can be used to demonstrate dissemination in space (DIS) within the 2017 McDonald criteria for the diagnosis of multiple sclerosis (MS). Objectives were (1) to assess whether optic nerve-MRI (ON-MRI), optical coherence tomography (OCT), and visual evoked potentials (VEP) detect optic nerve involvement in clinically isolated syndrome (CIS) and (2) to evaluate the contribution of the optic nerve topography to the current diagnostic criteria in a prospective, multicenter cohort., Methods: MAGNIMS centers were invited to provide prospective data on patients with CIS who underwent a visual assessment with at least 2 of 3 investigations (ON-MRI, OCT, or VEP) within 6 months of onset. Modified DIS criteria were constructed by adding the optic nerve topography, defined by each investigation separately and any combination of them, as the fifth area of the CNS. A risk assessment analysis and the performance of the different DIS criteria were analyzed using the diagnosis of MS according to the 2017 McDonald criteria as the primary outcome and new T2 lesions and/or a second relapse as the secondary outcome., Results: We included 157 patients with CIS from 5 MAGNIMS centers; 60/157 (38.2%) patients presented with optic neuritis. Optic nerve involvement on ON-MRI was found in 40.2% patients at study entry and in 72.5% of those with optic neuritis.At follow-up (mean 27.9 months, SD 14.5), 111/157 patients (70.7%) were diagnosed with MS according to the 2017 McDonald criteria. Fulfilling either 2017 DIS or any modified DIS criteria conferred a similar high risk for reaching primary and secondary outcomes. The modified DIS criteria had higher sensitivity (92.5% [with ON-MRI] vs 88.2%), but slightly lower specificity (80.0% [with GCIPL IEA ≥4 μm] vs 82.2%), with overall similar accuracy (86.6% [with ON-MRI] vs 86.5%) than 2017 DIS criteria. Consistent results were found for secondary outcomes., Discussion: In patients with CIS, the presence of an optic nerve lesion defined by MRI, OCT, or VEP is frequently detected, especially when presenting with optic neuritis. Our study supports the addition of the optic nerve as a fifth topography to fulfill DIS criteria.

Purpose: This study analyzes the main changes in retinal microcirculation in patients with multiple sclerosis (MS) and their relationship with the type of disease course., Material and Methods: 159 patients (318 eyes) were examined. The groups were formed according to the type of course and duration of MS: group 1 - 37 patients (74 eyes; 23.27%) with relapsing-remitting MS (RRMS) less than 1 year; group 2 - 47 patients (94 eyes; 29.56%) with RRMS from 1 year to 10 years; group 3 - 44 patients (86 eyes; 27.05%) with RRMS >10 years; group 4 - 32 patients (64 eyes; 20.12%) with secondary progressive MS (SPMS). Subgroups A and B were allocated within each group depending on the absence or presence of optic neuritis (ON). Patients underwent standard ophthalmological examination, including optical coherence tomography angiography (OCTA)., Results: A decrease in the vessel density (wiVD) and perfusion density (wiPD) in the macular and peripapillary regions was revealed, progressing with the duration of the disease and with its transition to the progressive type. The minimum values were observed in patients with SPMS (group 4), with the most pronounced in the subgroup with ON (wiVD = 16.06±3.65 mm/mm 2 , wiPD = 39.38±9.46%, ppwiPD = 44.06±3.09%, ppwiF = 0.41±0.05)., Conclusion: OCTA provides the ability to detect subclinical vascular changes and can be considered a comprehensive, reliable method for early diagnosis and monitoring of MS progression.

Background: Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) is a newly described clinical entity comprised of isolated or recurrent attacks of optic neuritis, transverse myelitis, acute disseminated encephalomyelitis (ADEM), encephalitis, or seronegative NMOSD. Prior studies report that 30-80 % of children and adults with MOGAD go on to have relapses though there are no reliable predictors. The objectives of this study were to (1) describe the demographic, clinical, and radiographic patterns of MOGAD at our center and (2) identify possible predictors of relapsing disease., Methods: Single-center retrospective cohort study of pediatric and adult subjects with MOGAD evaluated at least once at our center between January 1, 2017 and September 30, 2022. Eligible subjects had a history of positive MOG-IgG and consistent clinical syndrome comprised of an initial attack of optic neuritis (ON), transverse myelitis (TM), ADEM, cerebral cortical encephalitis, seronegative neuromyelitis optica (simultaneous ON and TM), isolated brainstem or cerebellar syndrome, or other (not fitting into another group). Relapsing subjects or those remaining monophasic at 12 months were included in the analyses of predictors of relapsing disease. Covariates included age, sex, race/ethnicity, and index event phenotype. Unadjusted and adjusted risk ratios were calculated for pediatric and adult subjects., Results: We describe the demographic, clinical, and radiographic characteristics of 58 subjects with MOGAD. Covariates from 48 subjects were analyzed for predictors of relapsing disease. In adults, Hispanics and non-White non-Hispanics were at increased risk of relapsing disease compared to non-Hispanic Whites [Adjusted RR 1.52 (95 % CI: 1.01, 2.30)]. There were no significant associations in the pediatric group., Conclusion: This study is the first to describe a cohort of MOGAD in the Pacific Northwest. Our findings highlight racial and ethnic differences in risk of relapsing MOGAD in adults. Further studies on racial and ethnic differences in MOGAD are needed to confirm these findings., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

Background: Hispanic people compared to White people with multiple sclerosis (MS) are two times more likely to present with optic neuritis (ON). ON in dissemination in space (DIS) after a single attack is not part of the current McDonald 2017 criteria., Objective: To evaluate if adding ON in DIS (ON-modified criteria) improves the performance of the McDonald 2017 criteria in the diagnosis of MS after a single attack of ON., Methods: Retrospective study of 102 patients of Hispanic background. Cases were reviewed between 2017 and 2021. Clinical ON was reported for 35 cases. ON in DIS was verified for 28 patients via MRI, optical coherence tomography, and/or visual evoked potential. We investigated the performance of the McDonald 2017 criteria and ON-modified criteria and calculated sensitivity, specificity, positive and negative predictive values, and accuracy., Results: The ON-modified criteria significantly improved the performance of the McDonald 2017 criteria ( p = 0.003) and identified an additional nine patients. Both sensitivity and accuracy increased from 64% to 74% and 62% to 71%, respectively, while specificity remained unchanged (40% (95% confidence interval (CI): 0.10, 0.70))., Conclusion: This study provides evidence that the inclusion of ON in DIS improved the overall performance of the McDonald 2017 criteria among Hispanic people., Competing Interests: Declaration of conflicting interestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: L.A. has research support from the National MS Society, NIH NINDS, Bristol Myer Squibb Foundation, Race to Erase MS Foundation, and Biogen Idec. She is a local PI for commercial trials funded by Genentech and Sanofi and Genzyme and receives consulting fees from Biogen Idec, Novartis, Genentech, and EMD Serono. M.V.R. receives research funding from the Robert A. Winn Diversity in Clinical Trials Awards Program founded by the Bristol Myers Squibb Foundation. He has received consulting fees from EMD Serono. D.S. is a local PI for a commercial trial funded by Novartis. O.M., A.M., and T.I. have no disclosures.

Purpose: Contrast-enhanced fluid-attenuated inversion recovery (FLAIR) sequence of the brain has the potential for detecting optic nerve abnormality. This study aimed to compare the diagnostic value of whole-brain contrast-enhanced three-dimensional FLAIR with fat suppression (CE 3D FLAIR FS) sequence in detecting acute optic neuritis to dedicated orbit MRI and clinical diagnosis., Materials and Methods: Twenty-two patients with acute optic neuritis who underwent whole-brain CE-3D-FLAIR FS and dedicated orbit MRI were retrospectively included. The hypersignal FLAIR of the optic nerve on whole-brain CE-3D-FLAIR FS, enhancement, and hypersignal T2W on orbit images were assessed. The optic nerve to frontal white matter signal intensity ratio on CE-FLAIR FS was calculated as maximum signal intensity ratio (SIR) and mean SIR., Results: Twenty-six hypersignals of optic nerves were found on CE-FLAIR FS from 30 pathologic nerves. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of CE FLAIR FS brain and dedicated orbital images for diagnosing acute optic neuritis were 77%, 93%, 96%, 65%, and 82% and 83%, 93%, 96%, 72%, and 86%, respectively. Optic nerve to frontal white matter SIR of the affected optic nerves was higher than that of normal optic nerves. Using a cutoff maximum SIR of 1.24 and cutoff mean SIR of 1.16, the sensitivity, specificity, PPV, NPV, and accuracy were 93%, 86%, 93%, 80%, and 89% and 93%, 86%, 93%, 86%, and 91%, respectively., Conclusion: The hypersignal of the optic nerve on whole-brain CE 3D FLAIR FS sequence has qualitative and quantitative diagnostic potential in patients with acute optic neuritis., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Optical coherence tomography angiography (OCTA) allows non-invasive assessment of retinal vessel structures. Thinning and loss of retinal vessels is evident in eyes of patients with multiple sclerosis (MS) and might be associated with a proinflammatory disease phenotype and worse prognosis. We investigated whether changes of the retinal vasculature are linked to brain atrophy and disability in MS., Material and Methods: This study includes one longitudinal observational cohort (n=79) of patients with relapsing-remitting MS. Patients underwent annual assessment of the expanded disability status scale (EDSS), timed 25-foot walk, symbol digit modalities test (SDMT), retinal optical coherence tomography (OCT), OCTA, and brain MRI during a follow-up duration of at least 20 months. We investigated intra-individual associations between changes in the retinal architecture, vasculature, brain atrophy and disability. Eyes with a history of optic neuritis (ON) were excluded., Results: We included 79 patients with a median disease duration of 12 (interquartile range 2 - 49) months and a median EDSS of 1.0 (0 - 2.0). Longitudinal retinal axonal and ganglion cell loss were linked to grey matter atrophy, cortical atrophy, and volume loss of the putamen. We observed an association between vessel loss of the superficial vascular complex (SVC) and both grey and white matter atrophy. Both observations were independent of retinal ganglion cell loss. Moreover, patients with worsening of the EDSS and SDMT revealed a pronounced longitudinal rarefication of the SVC and the deep vascular complex., Discussion: ON-independent narrowing of the retinal vasculature might be linked to brain atrophy and disability in MS. Our findings suggest that retinal OCTA might be a new tool for monitoring neurodegeneration during MS., Competing Interests: LA received travel and research support by Novartis Deutschland GmbH. RW received a poster grant from Novartis Deutschland GmbH. AB has received consulting and/or speaker fees from Alexion, Bayer Healthcare, Biogen, Celgene, Novartis Deutschland GmbH, Roche and Sandoz/Hexal. CM is a medical advisor to Heidelberg Engineering, Heidelberg, Germany, receives lecture honorarium by Heidelberg Engineering and Bayer AG, Leverkusen, Germany. CZ has served on scientific advisory boards for Philips and Bayer Schering; serves as co-editor on the Advisory Board of Clinical Neuroradiology; has received speaker honoraria from Bayer-Schering and Philips and has received research support and investigator fees for clinical studies from Biogen Idec, Quintiles, MSD Sharp & Dome, Boehringer Ingelheim, Inventive Health Clinical UK Ltd., Advance Cor, Brainsgate, Pfizer, Bayer-Schering, Novartis, Roche, Servier, Penumbra, WCT GmbH, Syngis, SSS Internartional Clinical Research, PPD Germany GmbH, Worldwide Clinical Trials Ltd., Phenox, Covidien, Actelion, Medivation, Medtronic, Harrison Clinical Research, Concentric, Penumbra, Pharmtrace, Reverse Medical Corp., Premier Research Germany Ltd., Surpass Medical Ltd. and GlaxoSmithKline. TK received travel support and speaking honoraria from Novartis Deutschland GmbH and Merck. BH has served on scientific advisory boards for Novartis Deutschland GmbH; he has served as DMSC member for AllergyCare, Sandoz, Polpharma and TG therapeutics; he or his institution have received speaker honoraria from Desitin; his institution received research grants from Regeneron for multiple sclerosis research. He holds part of two patents; one for the detection of antibodies against KIR4.1 in a subpopulation of patients with multiple sclerosis and one for genetic determinants of neutralizing antibodies to interferon. All conflicts are not relevant to the topic of the study. JK received speaking honoraria from Novartis Deutschland GmbH. BK received travel support and speaking honoraria from Novartis Deutschland GmbH, Teva, Heidelberg Engineering and served at the advisory board of Merck. He received a research grant from Novartis Deutschland GmbH. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2023 Romahn, Wiltgen, Bussas, Aly, Wicklein, Noll, Berthele, Dehmelt, Mardin, Zimmer, Korn, Hemmer, Kirschke, Mühlau and Knier.)

Optic neuritis, a characteristic feature of multiple sclerosis (MS), involves the inflammation of the optic nerve and the degeneration of retinal ganglion cells (RGCs). Although previous studies suggest that retinal blood flow alterations occur during optic neuritis, the precise location, the degree of impairment, and the underlying mechanisms remain unclear. In this study, we utilized two emerging non-invasive imaging techniques, laser speckle flowgraphy (LSFG) and optical coherence tomography angiography (OCTA), to investigate retinal vascular changes in a mouse model of MS, known as experimental autoimmune encephalomyelitis (EAE). We associated these changes with leukostasis, RGC injury, and the overall progression of EAE. LSFG imaging revealed a progressive reduction in retinal blood flow velocity and increased vascular resistance near the optic nerve head in the EAE model, indicating impaired ocular blood flow. OCTA imaging demonstrated significant decreases in vessel density, number of junctions, and total vessel length in the intermediate and deep capillary plexus of the EAE mice. Furthermore, our analysis of leukostasis revealed a significant increase in adherent leukocytes in the retinal vasculature of the EAE mice, suggesting the occurrence of vascular inflammation in the early development of EAE pathology. The abovechanges preceded or were accompanied by the characteristic hallmarks of optic neuritis, such as RGC loss and reduced visual acuity. Overall, our study sheds light on the intricate relationship between retinal vascular alterations and the progression of optic neuritis as well as MS clinical score. It also highlights the potential for the development of image-based biomarkers for the diagnosis and monitoring of optic neuritis as well as MS, particularly in response to emerging treatments.

Background: Studies have demonstrated that people with multiple sclerosis (pwMS) experience visual impairments and neurodegenerative retinal processes. The disability progression in pwMS may be associated with retinal changes assessed with optical coherence tomography (OCT). This meta-analysis aims at synthesizing the correlations between OCT measurements of disability in pwMS., Methods: We systematically searched four databases (PubMed/MEDLINE, Embase, Scopus, and Web of Science) from inception to November 2022, then conducted a meta-analysis using a random effects model to determine the pooled correlation coefficient(r) between OCT measurements and disability scales by R version 4.2.3 with the meta version 6.2-1 package., Results: From 3129 studies, 100 studies were included. Among 9051 pwMS, the female-to-male ratio was 3.15:1, with a mean age of 39.57 ± 6.07 years. The mean disease duration and Expanded Disability Status Scale (EDSS) were 8.5 ± 3.7 and 2.7 ± 1.1, respectively. Among the pooled subgroup analyses, macular ganglion cell inner plexiform layer (mGCIPL) in patients with relapsing-remitting (pwRRMS) and peripapillary retinal nerve fiber layer (pRNFL) in patients with progressive MS (pwPMS) had strong correlations with EDSS, r = -0.33 (95% CI: -0.45 to -0.20, I 2  = 45%, z-score = -4.86, p < 0.001) and r = -0.20 (95% CI:-0.58 to 0.26, I 2  = 76%, z-score = -0.85, p = 0.395), respectively. According to subgroup analysis on pwMS without optic neuritis (ON) history, the largest correlation was seen between EDSS and macular ganglion cell complex (mGCC): r = -0.39 (95% CI: -0.70 to 0.04, I 2  = 79%, z-score = -1.79, p = 0.073)., Conclusion: OCT measurements are correlated with disability in pwMS, and they can complement the comprehensive neurological visit as an additional paraclinical test., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest regarding the publication of this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Introduction: Impairment in visual and cognitive functions occur in youth with demyelinating disorders such as multiple sclerosis, neuromyelitis optica spectrum disorder, and myelin oligodendrocyte glycoprotein antibody-associated disease. Quantitative behavioral assessment using eye-tracking and pupillometry can provide functional metrics for important prognostic and clinically relevant information at the bedside., Methods: Children and adolescents diagnosed with demyelinating disorders and healthy, age-matched controls completed an interleaved pro- and anti-saccade task using video-based eye-tracking and underwent spectral-domain optical coherence tomography examination for evaluation of retinal nerve fiber layer and ganglion cell inner plexiform layer thickness. Low-contrast visual acuity and Symbol Digit Modalities Test were performed for visual and cognitive functional assessments. We assessed saccade and pupil parameters including saccade reaction time, direction error rate, pupil response latency, peak constriction time, and peak constriction and dilation velocities. Generalized Estimating Equations were used to examine the association of eye-tracking parameters with optic neuritis history, structural metrics, and visual and cognitive scores., Results: The study included 36 demyelinating disorders patients, aged 8-18 yrs. (75% F; median = 15.22 yrs., SD = 2.8) and 34 age-matched controls (65% F; median = 15.26 yrs., SD = 2.3). Surprisingly, pro- and anti-saccade performance was comparable between patients and controls, whereas pupil control was altered in patients. Oculomotor latency measures were strongly associated with the number of optic neuritis episodes, including saccade reaction time, pupil response latency, and peak constriction time. Peak constriction time was associated with both retinal nerve fiber layer and ganglion cell inner plexiform layer thickness. Pupil response latency and peak constriction time were associated with visual acuity. Pupil velocity for both constriction and dilation was associated with Symbol Digit Modalities Test scores., Conclusion: The strong associations between oculomotor measures with history of optic neuritis, structural, visual, and cognitive assessments in these cohorts demonstrates that quantitative eye-tracking can be useful for probing demyelinating injury of the brain and optic nerve. Future studies should evaluate their utility in discriminating between demyelinating disorders and tracking disease progression., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Isolated optic neuritis is a single episode inflammatory optic neuropathy. This condition, which affects the optimal function of the optic nerve, is not associated with neurological or systemic diseases. Our study aimed to compare patients with isolated optic neuritis and normal healthy individuals in terms of the cerebrum, cerebellum and hippocampus volumes by using the "volBrain Online MRI Brain Volumetry System" program. Persons diagnosed with isolated optic neuritis (n = 16) and persons without any disease (n = 16) were included in the study. VolBrain was used to process the MRI data and, the findings were compared with Mann-Whitney U test. Values with a p-value <0.05 were considered statistically significant. The cerebrum white matter volumes in the total brain and in the right-left hemispheres of the brain were statistically significantly lower in the optic neuritis group (p = 0.029; p = 0.050; p = 0.029, respectively). In the segmental cerebellum analysis, the left side lobule VIIIB, the total and right-left side lobule IX volumes were statistically significantly higher (p = 0.022; p = 0.014; p = 0.029; p = 0.018, respectively). In total, lobule I-II volume was statistically significantly lower in the optic neuritis group (p = 0.046). In the segmental hippocampus analysis, the right side CA2-CA3, the total and right-left side SR-SL-SM volumes were statistically significantly lower in the optic neuritis group (p = 0.039; p = 0.050; p = 0.016, respectively). There are neurodegenerative changes in brain volume in patients with isolated optic neuritis. Although volBrain alone is not sufficient to diagnose isolated optic neuritis, it provides quantitative data that can be used as a complementary diagnostic method., (© 2023 American Association of Clinical Anatomists and British Association of Clinical Anatomists.)

Background: Optic pathway is considered an ideal model to study the interaction between inflammation and neurodegeneration in multiple sclerosis (MS)., Methods: Optical Coherence Tomography (OCT) and 3.0 T magnetic resonance imaging (MRI) were acquired in 92 relapsing remitting (RR) MS at clinical onset. Peripapillary RNFL (pRNFL) and macular layers were measured. White matter (WM) and gray matter (GM) lesion volumes (LV), lateral geniculate nucleus (LGN) volume, optic radiations (OR) WM LV, thickness of pericalcarine cortex were evaluated. OCT and MRI control groups (healthy controls [HC]-OCT and HC-MRI) were included., Results: A significant thinning of temporal pRNFL and papillo-macular bundle (PMB) was observed (p<0.001) in 16 (17%) patients presented with monocular optic neuritis (MSON+), compared to 76 MSON- and 30 HC (-15 μm). In MSON-, PMB was reduced (-3 μm) compared to HC OCT (p<0.05). INL total volume was increased both in MSON+ (p<0.001) and MSON- (p = 0.033). Inner retinal layers volumes (macular RNFL, GCL and IPL) were significantly decreased in MSON+ compared to HC (p<0.001) and MSON- (p<0.001). Reduced GCL volume in the parafoveal ring was observed in MSON- compared to HCOCT (p < 0.05). LGN volume was significantly reduced only in MSON+ patients compared to HC-MRI (p<0.001) and MSON- (p<0.007). GCL, IPL and GCIP volumes associated with ipsilateral LGN volume in MSON+ and MSON-. Finally, LGN volume associated with visual cortex thickness with no significant difference between MSON+ and MSON-., Conclusions: Anterograde trans-synaptic degeneration is early detectable in RRMS presenting with optic neuritis but does not involve LGN., Competing Interests: Declaration of Competing Interest M.S., M.A., C.L., Mo.M., S.P., Pe.M., S.E., D.M., F.S., B.A. have no conflict to disclose. Ma.M. reports grants and personal fees from Almiral. She was awarded a MAGNIMS-ECTRIMS fellowship in 2020. Pu.M. reports grants from Almirall, Teva, Sanofi Genzyme, Merck Serono, Biogen Italy, Novartis, consultancy for Novartis, Biogen Italy, and Sanofi. G.P. reports grants from Almirall, Teva, Sanofi Genzyme, Merck Serono, Biogen Italy, Novartis, Roche, Bristol Myers Squibb; consultancy for Novartis, Biogen Italy, Sanofi Genzyme, Roche, Bristol Myers Squibb; board membership Sanofi Genzyme, Novartis, Biogen Italy, Roche, Merck Serono, Bristol Myers Squibb., (Copyright © 2023. Published by Elsevier B.V.)

Background and Objectives: The optic nerve has been recommended as an additional region for demonstrating dissemination in space (DIS) in diagnostic criteria for multiple sclerosis (MS). The aim of this study was to investigate whether adding the optic nerve region as determined by optical coherence tomography (OCT) as part of the DIS criteria improves the 2017 diagnostic criteria., Methods: From a prospective observational study, we included patients with a first demyelinating event who had complete information to assess DIS and a spectral domain OCT scan obtained within 180 days. Modified DIS criteria (DIS + OCT) were constructed by adding the optic nerve to the current DIS regions based on validated thresholds for OCT intereye differences. Time to second clinical attack was the primary endpoint., Results: We analyzed 267 patients with MS (mean age 31.3 years [SD 8.1], 69% female) during a median observation period of 59 months (range: 13-98). Adding the optic nerve as a fifth region improved the diagnostic performance by increasing accuracy (DIS + OCT 81.2% vs DIS 65.6%) and sensitivity (DIS + OCT 84.2% vs DIS 77.9%) without lowering specificity (DIS + OCT 52.2% vs DIS 52.2%). Fulfilling DIS + OCT criteria (≥2 of 5 DIS + OCT regions involved) indicated a similar risk of a second clinical attack (hazard ratio [HR] 3.6, CI 1.4-14.5) compared with a 2.5-fold increased risk when fulfilling DIS criteria (HR 2.5, CI 1.2-11.8). When the analysis was conducted according to topography of the first demyelinating event, DIS + OCT criteria performed similarly in both optic neuritis and nonoptic neuritis., Discussion: Addition of the optic nerve, assessed by OCT, as a fifth region in the current DIS criteria improves diagnostic performance by increasing sensitivity without lowering specificity., Classification of Evidence: This study provides Class II evidence that adding the optic nerve as determined by OCT as a fifth DIS criterion to the 2017 McDonald criteria improves diagnostic accuracy., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)

Background: Previous cross-sectional studies have reported distinct clinical and radiological features among the different acute optic neuritis (ON) aetiologies. Nevertheless, these reports often included the same number of patients in each group, not taking into account the disparity in frequencies of ON aetiologies in a real-life setting and thus, it remains unclear what are the truly useful features for distinguishing the different ON causes. To determine whether clinical evaluation, ophthalmological assessment including the optical coherence tomography (OCT), CSF analysis, and MRI imaging may help to discriminate the different causes of acute ON in a real-life cohort., Methods: In this prospective monocentric study, adult patients with recent acute ON (<1 month) underwent evaluation at baseline and 1 and 12 months, including, high- and low-contrast visual acuity, visual field assessment and OCT measurements, baseline CSF analysis and MRI., Results: Among 108 patients, 71 (65.7%) had multiple sclerosis (MS), 19 (17.6%) had idiopathic ON, 13 (12.0%) and 5 (4.6%) had myelin oligodendrocyte glycoprotein and aquaporin-4 antibodies, at last follow up respectively.At baseline, the distribution of bilateral ON, CSF-restricted oligoclonal bands, optic perineuritis, optic nerve length lesions and positive dissemination in space and dissemination in time criteria on MRI were significantly different between the four groups (p <0.001). No significant difference in visual acuity nor inner retinal layer thickness was found between the different ON aetiologies., Conclusions: In this large prospective study, bilateral visual involvement, CSF and MRI results are the most useful clues in distinguishing the different aetiologies of acute ON, whereas ophthalmological assessments including OCT measurements revealed no significant difference between the aetiologies., Competing Interests: Declaration of Competing Interest No disclosure relevant to the manuscript., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background and Objectives: The clinical spectrum of myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease (MOGAD) is heterogenous and has evolved over time since the commercial availability of the anti-MOG antibody assay. Subclinical disease activity has been previously reported in the visual pathway, but prevalence data remains limited. We investigated subclinical optic neuritis (ON) based on changes on retinal nerve fiber layer (RNFL) thickness on optic coherence tomography (OCT) in pediatric patients who tested positive for the anti-MOG antibody., Methods: In this retrospective, single-center cohort study, we examined children with MOGAD with at least one complete assessment of the anterior visual pathway. Subclinical ON was defined by structural visual system disease in the absence of a subjective complaint of vision loss, pain (particularly with eye movement), or color desaturation., Results: Records were reviewed from 85 children with MOGAD, 67 of whom (78.8%) had complete records for review. Eleven children (16.4%) had subclinical ON on OCT. Ten had significant reductions in RNFL, of which one had two distinct episodes of decreased RNFL, and one had significant elevations in RNFL. Of the eleven children with subclinical ON, six (54.5%) had a relapsing disease course. We also highlighted the clinical course of three children with subclinical ON detected on longitudinal OCT, including two who had subclinical ON outside of clinical relapses., Conclusion: Children with MOGAD can have subclinical ON events that can manifest as significant reductions or elevations in RNFL on OCT. OCT should be used routinely in the management and monitoring of MOGAD patients., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: The multi-order visual system represents an excellent testing site regarding the process of trans-synaptic degeneration. The presence and extent of global versus trans-synaptic neurodegeneration in people with multiple sclerosis (pwMS) is not clear., Objective: To explore cross-sectional and longitudinal relationships between retinal, thalamic and cortical changes in pwMS with and without MS-related optic neuritis (pwMSON and pwoMSON) using MRI and optical coherence tomography (OCT)., Methods: 162 pwMS and 47 healthy controls (HCs) underwent OCT and brain MRI at baseline and 5.5-years follow-up. Peripapillary retinal nerve fiber layer (pRNFL) and macular ganglion cell inner plexiform layer (mGCIPL) thicknesses were determined. Global volume measures of brain parenchymal volume (BPV)/percent brain volume change (PBVC), thalamic volume and T2-lesion volume (LV) were derived using standard analysis protocols. Regional cortical thickness was determined using FreeSurfer. Cross-sectional and longitudinal relationship between the retinal measures, thalamic volume and cortical thickness were assessed using age, BPV/PBVC and T2-LV adjusted correlations and regressions., Results: After age, BPV and T2-LV adjustment, the thalamic volume explained additional variance in the thickness of pericalcarine (R 2 increase of 0.066, standardized β = 0.299, p = 0.039) and lateral occipital (R2 increase of 0.024, standardized β = 0.299, p = 0.039) gyrii in pwMSON. In pwoMSON, the thalamic volume was a significant predictor only of control (frontal) regions of pars opercularis. There was no relationship between thalamic atrophy and cortical thinning over the follow-up in both pwMS with and without MSON. While numerically lower in the pwMSON group, the inter-eye difference was not able to predict the presence of MSON., Conclusions: MSON can induce a measurable amount of trans-synaptic pathology on second-order cortical regions., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Aim: To investigate the structural and functional magnetic resonance imaging (MRI) alterations and their clinical significance for predicting visual outcomes at 3 years in clinically isolated optic neuritis (CION)., Materials and Methods: Forty-three CION patients and 44 matched healthy controls (HC) underwent a three dimensional (3D) T1-weighted and resting-state functional MRI using a 3 T MRI system. Grey-matter volume (GMV) and functional MRI measures were compared among HC and CION patients with good and poor outcomes. The correlations between MRI measures and visual outcomes were investigated, and a binary logistic regression model was performed to predict the visual outcome., Results: CION patients with good and poor outcomes showed similar patterns of decreased GMV and increased functional MRI activities compared to HC. Compared to patients with good visual recovery, CION patients with poor visual recovery showed significantly reduced GMV in the insula and superior temporal gyrus (STG), decreased amplitude of low-frequency fluctuation (ALFF) in the inferior frontal gyrus (IFG), and increased functional activities in the middle frontal gyrus (MFG) and middle temporal gyrus (MTG). Binary logistic regression analysis predicted poor visual recovery, including decreased GMV in the bilateral insula (right insula: odds ratio [OR] = 17.46, p<0.001; left insula: OR=10.538, p=0.001; respectively) and STG (OR=16.551, p<0.001) and increased ALFF (OR=17.148, p<0.001) and regional homogeneity (OR=10.068, p=0.002) in the left MTG., Conclusion: CION patients showed decreased GMV and increased functional activities predominantly located in visual- and cognition-related areas. Decreased GMV and increased ALFF or regional homogeneity in the high-order visual regions (insula, STG, and MTG) are promising imaging markers predicting poor visual outcomes at the 3-year follow-up., (Copyright © 2023. Published by Elsevier Ltd.)

Background: Optic neuritis (ON) is an inflammatory disease of optic nerve. The distinct etiologies of ON significantly influence its clinical manifestation, neuroimaging findings, and visual outcomes. However, the clinical characteristics might be influenced by the racial differences. The purpose of this study is to investigate the clinical characteristics of various types of ON at a Taiwanese tertiary center., Methods: This cohort study analyzed 163 patients who received treatment and continued following-up for ON between 2015 and 2022. We selected patients who had been tested for anti-aquaporin-4 antibody (AQP4-Ab) and anti-myelin oligodendrocyte glycoprotein antibody (MOG-Ab). The participants were classified into four groups on the basis of their etiologies, specifically (1) multiple sclerosis (MS)-related, (2) AQP4-Ab-positive, (3) MOG-Ab-positive, or (4) idiopathic ON. The researchers recorded the patients' clinical characteristics, treatment course, magnetic resonance imaging and optical coherence tomography (OCT) findings, and visual outcomes., Results: MOG-Ab-positive group had higher percentages of disk swelling and pain with eye movement. Long optic nerve and perineural enhancement are the hallmarks of MOG-Ab-related ON. The ON relapse rate was higher in AQP4-Ab-positive group. Although members of AQP4-Ab-positive group received immediate steroid pulse therapy, these patients experienced the worst visual outcomes. Moreover, a thinner retinal nerve fiber layer (RNFL) was noted in AQP4-Ab-positive group. MS group had a higher incidence of extra-optic nerve lesions. Multivariate regression identified pretreatment visual acuity and RNFL thickness as the important factors affecting visual outcomes., Conclusions: This cohort study identified the clinical features of different types of ON. Patients with AQP4-Ab-positive ON had poorer visual outcomes, which may be attributed to multiple relapses and profound nerve damage, as revealed by OCT findings. Patients with MOG-Ab-positive ON displayed long optic nerve enhancement but had more favorable prognoses. Thus, antibody-based classification facilitates treatment and prognosis in ON., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023 Elsevier B.V. All rights reserved.)