Myelin oligodendrocyte glycoprotein (MOG) associated optic neuritis in a patient with idiopathic intracranial hypertension (IIH) and compressive optic neuropathy case report.

BACKGROUND: Myelin oligodendrocyte glycoprotein-associated disease (MOGAD) has a wide phenotypic expression and should be considered in a differential diagnosis of patients with optic disc edema and increased intracranial pressure because MOGAD can mimic IIH and compressive optic neuropathy. CASE PRESENTATION: A 53-year-old woman with a history of presumed idiopathic intracranial hypertension ("IIH") presented with new headache and visual loss. She had a BMI of 35.44 kg/m2 and a past medical history significant for depression, hepatitis C, hyperlipidemia, and uterine cancer post-hysterectomy. She had undergone multiple lumboperitoneal shunts for presumed IIH and had a prior pituitary adenoma resection. Her visual acuity was no light perception OD and counting fingers OS. After neuro-ophthalmic consultation, a repeat cranial MRI showed symmetric thin peripheral optic nerve sheath enhancement of the intra-orbital optic nerves OU. Serum MOG antibody was positive at 1:100 and she was treated with intravenous steroids followed by plasma exchange and rituximab. CONCLUSIONS: This case highlights the importance of considering MOGAD in the differential diagnosis of optic neuropathy. Although likely multifactorial, we believe that the lack of improvement in our case from presumed IIH and despite adequate neurosurgical decompression of a pituitary adenoma with compression of the optic apparatus reflected underlying unrecognized MOGAD. Clinicians should consider repeat imaging of the orbit (in addition to the head) in cases of atypical IIH or compressive optic neuropathy especially when the clinical course or response to therapy is poor or progressive.

Clinical profile and challenges faced in the management of optic neuritis: the Indian scenario.

PURPOSE: Optic neuritis (ON) is a relatively common ophthalmic disease that has recently received renewed attention owing to immunological breakthroughs. We studied the profile of patients with ON with special reference to antibody-mediated ON and the challenges faced in its management. METHODS: Case records of patients with ON presenting to a tertiary eye-care center in South India were analyzed. Data on demographics, presenting visual acuity (VA), clinical features, seropositivity for aquaporin-4 immunoglobulin G (AQP4-IgG) and myelin oligodendrocyte glycoprotein immunoglobulin G (MOG-IgG), details of magnetic resonance imaging (MRI) of orbits and brain, and treatment were collected. RESULTS: Among 138 cases with acute ON, male: female ratio was 1:2. Isolated ON was present in 41.3% of cases. Antibody testing of sera was performed in 68 patients only due to financial limitations. Among these, 48.5% were MOG-IgG-seropositive, 11.76% were AQP4-IgG-seropositive, and 30.88% samples were double seronegative. Other causes included multiple sclerosis (n = 4), lactational ON (n = 4), tuberculosis (n = 2), invasive perineuritis (n = 2), COVID-19 vaccination (n = 2), and COVID-19 (n = 1). The mean presenting best corrected visual acuity (BCVA) was 1.31 ± 1.16 logMAR (logarithm of the minimum angle of resolution). The mean BCVA at 3 months was 0.167 ± 0.46 logMAR. Only initial VA ≤ 'Counting fingers' (CF) had a significant association with the visual outcome for final VA worse than CF. The steep cost of investigations and treatment posed challenges for many patients in the management of ON. CONCLUSION: MOG-IgG-associated ON is common in India. Unfortunately, financial constraints delay the diagnosis and timely management of ON, adversely affecting the outcome.

Batoclimab as an add-on therapy in neuromyelitis optica spectrum disorder patients with acute attacks.

BACKGROUND AND PURPOSE: Neuromyelitis optica spectrum disorder (NMOSD) is a severe neurological inflammatory disease mainly caused by pathogenic aquaporin-4 antibodies (AQP4-IgG). The safety and efficacy of the neonatal Fc receptor antagonist batoclimab addition to conventional intravenous methylprednisolone pulse (IVMP) therapy in patients with NMOSD acute attacks was assessed. METHODS: In an open-label, dose-escalation phase 1b study, NMOSD patients with acute myelitis and/or optic neuritis received four doses of weekly subcutaneous injections of either 340 mg or 680 mg batoclimab with concurrent IVMP and were followed up for 27 weeks. The primary end-points were safety and tolerability. Secondary end-points included pharmacodynamics and efficacy, with key efficacy assessment at week 4. RESULTS: In total nine NMOSD patients were enrolled, including two and seven in the 340 and 680 mg groups. Five patients had acute myelitis, while the remaining four had unilateral optic neuritis. Batoclimab add-on therapy had an overall good safety profile without serious adverse events. In the 680 mg group, mean immunoglobulin G (IgG) reached its maximum reduction at the last dose (day 22). In the meantime, AQP4-IgG was undetectable in six of seven subjects whose baseline AQP4-IgG titers ranged from 1:32 to 1:320. Expanded Disability Status Scale score was reduced by 1.3 ± 0.4 at week 4 (2.7 ± 1.3) compared with baseline (4.0 ± 1.0). CONCLUSIONS: Batoclimab add-on therapy to IVMP is safe and tolerated in patients with NMOSD. Preliminary evidence suggests a beneficial neurological effect. A randomized controlled trial would be needed to prove the efficacy.

A Randomized Prospective Trial Comparing Repository Corticotropin Injection and Intravenous Methylprednisolone for Neuroprotection in Acute Optic Neuritis.

BACKGROUND: Repository corticotrophin injection (RCI, Acthar Gel) and intravenous methylprednisolone (IVMP) improve the rate but not the extent of visual recovery following acute optic neuritis. RCI has adrenal-stimulating and melanocortin receptor-stimulating properties that may endow it with unique anti-inflammatory properties relative to IVMP. METHODS: Individuals with acute optic neuritis of less than 2 weeks duration were prospectively enrolled and randomized 1:1 to receive either RCI or IVMP. Peripapillary retinal nerve fiber layer (pRNFL) and ganglion cell plus inner plexiform layer thickness (GC + IPL) were serially evaluated by OCT. In addition, patient-reported outcomes (PROs) for changes in fatigue, mood, visual function, depression, and quality of life (QOL) were measured, and high and low contrast visual acuity were recorded. RESULTS: Thirty-seven subjects were enrolled (19 RCI; 18 IVMP); the average time from symptom to treatment was 8.8 days. At 6 months, there was no difference in the primary outcome: loss of average pRNFL thickness in the affected eye (RCI vs IVMP: -13.1 vs -11.7 µm, P = 0.88) 6 months after randomization. Additional outcomes also showed no difference between treatment groups: 6-month attenuation of GC + IPL thickness (RCI vs IVMP: -13.8 vs -12.0 µm, P = 0.58) and frequency of pRNFL swelling at 1 month (RCI vs IVMP: 63% vs 72%, P = 0.73) and 3 months (RCI vs IVMP: 26% vs 31%, P = 0.99). Both treatments resulted in improvement in visual function and PROs. CONCLUSIONS: Treatment of acute optic neuritis with RCI or IVMP produced no clinically meaningful differences in optic nerve structure or visual function.

Predictors of Long-Term Visual Acuity in a Modern Cohort of Patients With Acute Idiopathic and Multiple Sclerosis-Associated Optic Neuritis.

BACKGROUND: For patients with idiopathic or multiple sclerosis (MS)-associated optic neuritis (ON), the largest multicenter clinical trial (Optic Neuritis Treatment Trial [ONTT]) showed excellent visual outcomes and baseline high-contrast visual acuity (HCVA) was the only predictor of HCVA at 1 year. We aimed to evaluate predictors of long-term HCVA in a modern, real-world population of patients with ON and compare with previously published ONTT models. METHODS: We performed a retrospective, longitudinal, observational study at the University of Michigan and the University of Calgary evaluating 135 episodes of idiopathic or MS-associated ON in 118 patients diagnosed by a neuro-ophthalmologist within 30 days of onset (January 2011-June 2021). Primary outcome measured was HCVA (Snellen equivalents) at 6-18 months. Multiple linear regression models of 107 episodes from 93 patients assessed the association between HCVA at 6-18 months and age, sex, race, pain, optic disc swelling, symptoms (days), viral illness prodrome, MS status, high-dose glucocorticoid treatment, and baseline HCVA. RESULTS: Of the 135 acute episodes (109 Michigan and 26 Calgary), median age at presentation was 39 years (interquartile range [IQR], 31-49 years), 91 (67.4%) were women, 112 (83.0%) were non-Hispanic Caucasians, 101 (75.9%) had pain, 33 (24.4%) had disc edema, 8 (5.9%) had a viral prodrome, 66 (48.9%) had MS, and 62 (46.6%) were treated with glucocorticoids. The median (IQR) time between symptom onset and diagnosis was 6 days (range, 4-11 days). The median (IQR) HCVA at baseline and at 6-18 months were 20/50 (20/22, 20/200) and 20/20 (20/20, 20/27), respectively; 62 (45.9%) had better than 20/40 at baseline and 117 (86.7%) had better than 20/40 at 6-18 months. In linear regression models (n = 107 episodes in 93 patients with baseline HCVA better than CF), only baseline HCVA (ß = 0.076; P = 0.027) was associated with long-term HCVA. Regression coefficients were similar and within the 95% confidence interval of coefficients from published ONTT models. CONCLUSIONS: In a modern cohort of patients with idiopathic or MS-associated ON with baseline HCVA better than CF, long-term outcomes were good, and the only predictor was baseline HCVA. These findings were similar to prior analyses of ONTT data, and as a result, these are validated for use in conveying prognostic information about long-term HCVA outcomes.

SARS-CoV-2 Parainfectious Optic Neuropathy: 3 Case Reports and a Review of the Literature.

BACKGROUND: Parainfectious optic neuritis is an inflammatory reaction that occurs shortly after an infection without direct invasion by a pathogen. The clinical profile depends on the infectious organism. Cases of SARS-CoV-2 parainfectious optic neuritis have been reported in the literature, but there are no reviews that have applied strict inclusion criteria to more definitively establish the clinical profile associated with SARS-CoV-2. METHODS: We present 3 new cases of SARS-CoV-2 parainfectious optic neuritis. We also review the literature for definite cases by selecting only those with unambiguous clinical features and MRI findings of optic neuritis, positive SARS-CoV-2 polymerase chain reaction or serology, and the absence of myelin oligodendrocyte-glycoprotein or aquaporin-4 antibodies or other diseases associated with optic neuritis. RESULTS: We report 2 cases of monophasic, unilateral SARS-CoV-2 parainfectious optic neuritis with optic disc edema and nadir visual acuities of finger counting. We report 1 case of mild SARS-CoV-2 parainfectious optic neuritis that featured cotton wool spots, peripapillary wrinkles and hemorrhages, and recurrence after an initial steroid taper. We identified 6 cases of unambiguous SARS-CoV-2 parainfectious optic neuritis from the literature. Combining our case series with the case reports in the literature, the average age was 42.8 years, 3/9 had bilateral disease, 6/8 had optic disc edema, 8/9 had nadir visual acuity of finger counting or worse, and all recovered visual acuity to 20/40 or better after therapy with steroids. CONCLUSIONS: SARS-CoV-2 parainfectious optic neuritis has a clinical profile that is atypical for idiopathic optic neuritis but fairly typical of parainfectious forms of optic neuritis with a severely reduced nadir visual acuity, high likelihood of bilaterality, high incidence of optic disc edema, and prompt and significant response to corticosteroids. Further study with long-term follow-up and epidemiologic investigation will be needed to further characterize this clinical entity.

Failure of alemtuzumab therapy in three patients with MOG antibody associated disease.

BACKGROUND: Myelin Oligodendrocyte Glycoprotein antibody-associated disease (MOGAD) is most classically associated in both children and adults with phenotypes including bilateral and recurrent optic neuritis (ON) and transverse myelitis (TM), with the absence of brain lesions characteristic of multiple sclerosis (MS). ADEM phenotype is the most common presentation of MOGAD in children. However, the presence of clinical phenotypes including unilateral ON and short TM in some patients with MOGAD may lead to their misdiagnosis as MS. Thus, clinically and radiologically, MOGAD can mimic MS and clinical vigilance is required for accurate diagnostic workup. CASE PRESENTATION: We present three cases initially diagnosed as MS and then treated with alemtuzumab. Unexpectedly, all three patients did quite poorly on this medication, with a decline in their clinical status with worsening of expanded disability status scale (EDSS) and an increasing lesion load on magnetic resonance imaging of the brain. Subsequently, all three cases were found to have anti-MOG antibody in their serum. CONCLUSIONS: These cases highlight that if a patient suspected to have MS does not respond to conventional treatments such as alemtuzumab, a search for alternative diagnoses such as MOG antibody disease may be warranted.

Acute disseminated encephalomyelitis with bilateral optic neuritis following ChAdOx1 COVID-19 vaccination.

BACKGROUND: Acute disseminated encephalomyelitis (ADEM) is a rare immune-mediated inflammatory demyelinating disease of the central nervous system. We report a case of ADEM presenting with bilateral optic neuritis temporally associated with the ChAdOx1 vaccine against SARS-COVID19 virus. CASE PRESENTATION: A 36-year-old female presented with bilateral optic neuritis following her first dose of the ChAdOx1 vaccine. Initial MRI Brain showed evidence of demyelination within the subcortical white matter, with no radiological involvement of the optic nerves. Visual evoked potentials were consistent with bilateral optic neuritis which was confirmed radiologically on follow up MRI. She was treated with intravenous steroids with improvement both in symptoms and radiological appearance. A pseudo-relapse occurred which was treated with a further course of intravenous steroids followed by an oral taper. The clinical, radiological and serological results were most consistent with diagnosis of ADEM. CONCLUSIONS: ADEM is an exceedingly rare complication of ChAdOx1 vaccine despite millions of doses. While it is imperative clinicians remain aware of neurological complications of vaccines, the importance of vaccination to control a pandemic should not be undermined.

Optic perineuritis.

PURPOSE OF REVIEW: This review paper aims at discussing pathogenesis, etiology, clinical features, management, and prognosis of OPN. RECENT FINDINGS: Optic perineuritis (OPN) is an inflammatory process primarily involving the optic nerve sheath. Clinically, OPN usually presents with unilateral, gradual decline of visual function, eye pain, and/or pain on eye movements, disc edema and various features of optic nerve dysfunction, including visual field defects. It can mimic typical optic neuritis. In most cases of OPN, the disease is isolated with no specific etiology being identified, however, it can also occur secondary to a wide range of underlying systemic diseases. OPN is clinically diagnosed and radiologically confirmed based on the finding of circumferential perineural enhancement of the optic nerve sheath on magnetic resonance imaging (MRI). SUMMARY: Unlike optic nerve, OPN is not typically self-limited without treatment. High-dose oral corticosteroids are the mainstay of treatment in OPN. The initiation of therapy usually causes rapid and dramatic improvement in signs and symptoms. In general, OPN usually has a relatively good visual prognosis, which is influenced by delays between the onset of visual loss and the initiation of steroid therapy as well as the presence of underlying systemic diseases.

Unilateral optic neuritis after vaccination against the coronavirus disease: two case reports.

BACKGROUND: Due to the emergence of COVID-19, many countries have started mass immunization programs. To date, no cases of optic neuritis following COVID-19 vaccination have been reported in the literature. CASE PRESENTATION: Objective: Here, we report 2 cases of unilateral optic neuritis after vaccination against COVID-19 using the Sinopharm vaccine (Sinopharm Group Co. Ltd, China). DESIGN: The clinical history, examination, and test findings of two individuals with unilateral optic neuritis associated with the timing of COVID-19 vaccination were described and further analyzed. SETTING: Two patients developed optic neuritis after receiving the COVID-19 vaccine. One patient developed optic neuritis 6 weeks after the first dose and 3 weeks after the second dose. The other patient developed optic neuritis 3 weeks after the first dose. PARTICIPANTS: Two female patients, aged 21 and 39 years. RESULT: The patients were successfully treated with intravenous methylprednisolone pulse therapy. Both patients had typical manifestations of optic neuritis and their visual acuity recovered fully after treatment. The second of these patients was positive for anti-myelin oligodendrocyte glycoprotein antibodies (MOG). CONCLUSION: Optic neuritis is a potential adverse effect after vaccination against the coronavirus disease (COVID-19).

Memantine administration in patients with optic neuritis: a double blind randomized clinical trial.

INTRODUCTION: As an inflammatory phenomenon, optic neuritis (ON) that causes demyelination in the optic nerve damages the retinal cells, and leads to visual impairment. Herein, we aimed to investigate the potential therapeutic effects of memantine on ON. METHODS: In this double-blinded randomized clinical trial, participants with the first episode of acute ON meeting the inclusion criteria were enrolled and were randomly divided into memantine group (MG; N = 20) and placebo group (PG; N = 18). Patients of MG received memantine for 6 weeks. The thickness of the retinal nerve fiber layer (RNFL), visual evoked potential (VEP), and visual acuity (VA) was measured in both groups at baseline and 3-month follow-up. RESULTS: Thirty-eight patients with ON were enrolled. In the follow-up, mean RNFL thickness of both groups significantly decreased in all quadrants (P < 0.001). Also, RNFL thickness of all but temporal quadrants were significantly higher in the MG than placebo. The reduction in RNFL thickness difference was insignificant between two groups in all but the inferior quadrant which was significantly lower in MG (P = 0.024). In follow-up, mean-to-peak of P100 of the affected eye were significantly lowered (P < 0.001). The changes in VEP were insignificant. Originally, the mean VA was 0.15 ± 0.08 and 0.17 ± 0.09 in MG and PG, respectively, but was improved significantly to 0.92 ± 0.06 and 0.91 ± 0.06 in MG and PG, respectively, in follow-up. CONCLUSION: Memantine can reduce the RNFL thinning in three quadrants by blocking NMD receptors. However, visual acuity did not show a significant difference between the two groups.

Orbital Inflammation in Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disease: A Case Report and Review of the Literature.

BACKGROUND: To present 2 patients with myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease with unilateral orbital inflammation, optic nerve head edema, and abnormalities of the optic nerve and nerve sheath on imaging. We review the most current literature on this important and uncommon clinical phenotype. METHODS: A case report of 2 patients and a comprehensive review of the relevant literature on orbital inflammation in MOG antibody-associated disease (MOG-AD). RESULTS: Two patients presented with decreased vision and unilateral orbital inflammation. Both had optic nerve head edema and abnormalities of the optic nerve and nerve sheath on imaging. The patients were treated with immunosuppressants and had improvement of vision changes as well as their orbital inflammatory signs. MOG antibody was positive in high titers in both patients. Only 3 other cases of orbital inflammation associated with MOG antibody have been described. In all cases, orbital signs responded rapidly to intravenous methylprednisolone, but the improvement in visual acuity was variable and less robust. CONCLUSION: Orbital inflammation is a unique and underrecognized phenotype of MOG-AD with only a few reports in the literature. In patients who present with vision loss and orbital inflammation, MOG-AD should be considered in the differential.

The Treatment of Myelin Oligodendrocyte Glycoprotein Antibody Disease: A State-of-the-Art Review.

BACKGROUND: Myelin oligodendrocyte glycoprotein antibody disease (MOGAD) is an important etiology of neurologic morbidity and specifically, atypical, and relapsing optic neuritis. This review summarizes acute treatment and long-term prevention approaches in MOGAD. EVIDENCE ACQUISITION: PubMed and Google Scholar databases were manually searched and reviewed. RESULTS: We review the evidence base for acute treatment of MOGAD with corticosteroids and adjunct therapies, such as intravenous immunoglobulin (IVIg) and plasma exchange. We discuss the utility of prolonged corticosteroid tapering after the acute attack. We then summarize the commonly used disease-modifying treatments for relapsing MOGAD, including chronic low-dose corticosteroids, classic antirheumatic immune suppressants, biologic agents, and IVIg. CONCLUSIONS: While acute MOGAD attacks are usually treated with high-dose IV corticosteroids, longer oral corticosteroid tapers may prevent rapid relapse. Multiple long-term treatment strategies are being employed in recurrent MOGAD, with IVIg is emerging as probably the most effective therapy.

ABCB1 gene polymorphisms impact the effect of high-dose intravenous methylprednisolone therapy on optic neuritis associated with AQP4-IgG-positive neuromyelitis optica spectrum disorder.

WHAT IS KNOWN AND OBJECTIVE: Patients with optic neuritis (ON) have significant individual differences in their response to high-dose intravenous methylprednisolone (HIMP) therapy. This study aims to evaluate the association between gene polymorphisms and the efficacy of HIMP therapy in Chinese Han patients with ON mediated by aquaporin-4 immunoglobulin G antibody (AQP4-IgG) -positive neuromyelitis optica spectrum disorder (NMOSD) or multiple sclerosis (MS). METHODS: Chinese Han patients with AQP4-IgG+ NMOSD-ON or MS-ON were genotyped for four candidate genes: ABCB1 (rs1045642, rs1128503, rs2032582), NR3C1 (rs41423247), TBX21 (rs9910408, rs16947078) and VDR (rs731236, rs1544410, rs7975232, rs2228570). Patients were divided into glucocorticoid resistance (GR) and glucocorticoid sensitivity (GS) groups based on vision acuity (VA) improvement after HIMP treatment. Intergroup comparisons were performed on clinical characteristics, allele and genotype frequencies and haplotype distributions. RESULTS: A total of 267 patients completed the follow-up, including 120 patients with AQP4-IgG+ NMOSD-ON and 147 patients with MS-ON. We observed a significant association between the ABCB1 G2677T/A (rs2032582) polymorphism and glucocorticoid response in AQP4-IgG+ NMOSD-ON patients. Changes in VA scores in patients with the GG genotype were significantly lower than those in patients with the T/A T/A genotype (1.07 ± 1.20 vs. 1.77 ± 1.31, p = 0.026). In the GS group, the G allele had a lower frequency than the T/A allele (32.03% vs. 60.16%, p = 0.001). Logistic regression analysis showed that the G2677T/A GG and G T/A genotypes could increase the GR risk 3.53 and 2.67 times compared with the T/A T/A genotype, respectively (OR = 3.534, 95% CI: 1.186-10.527, p = 0.023; OR = 2.675, 95% CI: 1.005-7.123, p = 0.049). In addition, haplotype analysis showed that AQP4-IgG+ NMOSD-ON patients with the TAT/TTT haplotype (ABCB1 C3435T-G2677T/A-C1236T) were only 0.54 times more likely to develop GR than those with other haplotypes (OR = 0.542, 95% CI: 0.315-0.932, p = 0.026). However, we did not observe intergroup differences in the MS-ON population. WHAT IS NEW AND CONCLUSION: Our findings suggest that the G > T/A polymorphism of ABCB1 G2677T/A and the TAT/TTT haplotype played a protective role in HIMP treatment of AQP4-IgG+ NMOSD-ON but not MS-ON.

Systematic Review of Erythropoietin (EPO) for Neuroprotection in Human Studies.

Erythropoietin (EPO) is an exciting neurotherapeutic option. Despite its potential, concerns exist regarding the potential for thrombosis and adverse events with EPO administration in normonemic adults. Systematic review of literature using PRISMA guidelines to examine the application and risks of EPO as a treatment option for neuroprotection in normonemic adults. Independent, systematic searches were performed in July 2019. PubMed (1960-2019) and the Cochrane Controlled Trials Register (1960-2019) were screened. Search terms included erythropoietin, neuroprotection, and humans. The PubMed search resulted in the following search strategy: ("erythropoietin" [MeSH Terms] OR "erythropoietin" [All Fields] OR "epoetin alfa" [MeSH Terms] OR ("epoetin" [All Fields] AND "alfa" [All Fields]) OR "epoetin alfa" [All Fields]) AND ("neuroprotection" [MeSH Terms] OR "neuroprotection" [All Fields]) AND "humans" [MeSH Terms]. PubMed, Cochrane Controlled Trials Register, and articles based on prior searches yielded 388 citations. 50 studies were included, comprising of 4351 patients. There were 13 studies that noted adverse effects from EPO. Three attributed serious adverse effects to EPO and complications were statistically significant. Two of these studies related the adverse events to the co-administration of EPO with tPA. Minor adverse effects associated with the EPO group included nausea, pyrexia, headache, generalized weakness and superficial phlebitis. Most published studies focus on spinal cord injury, peri-surgical outcomes and central effects of EPO. We found no studies to date evaluating the role of EPO in post-operative pain. Future trials could evaluate this application in persistent post-surgical pain and in the peri-operative period.

Neurofilament results for the phase II neuroprotection study of phenytoin in optic neuritis.

BACKGROUND: A randomized trial of phenytoin in acute optic neuritis (ON) demonstrated a 30% reduction in retinal nerve fiber layer (RNFL) loss with phenytoin versus placebo. Here we present the corresponding serum neurofilament analyses. METHODS: Eighty-six acute ON cases were randomized to receive phenytoin (4-6 mg/kg/day) or placebo for 3 months, and followed up for 6 months. Serum was collected at baseline, 3 and 6 months for analysis of neurofilament heavy chain (NfH) and neurofilament light chain (NfL). RESULTS: Sixty-four patients had blood sampling. Of these, 58 and 56 were available at 3 months, and 55 and 54 were available at 6 months for NfH and NfL, respectively. There was no significant correlation between serum NfH and NfL at the time points tested. For NfH, the difference in mean placebo - phenytoin was -44 pg/ml at 3 months (P = 0.019) and -27 pg/ml at 6 months (P = 0.234). For NfL, the difference was 1.4 pg/ml at 3 months (P = 0.726) and -1.6 pg/ml at 6 months (P = 0.766). CONCLUSIONS: At 3 months, there was a reduction in NfH, but not NFL, in the phenytoin versus placebo group, while differences at 6 months were not statistically significant. This suggests a potential neuroprotective role for phenytoin in acute ON, with the lower NfH at 3 months, when levels secondary to degeneration of the anterior visual pathway are still elevated, but not at 6 months, when levels have normalized.

Late-onset acute disseminated encephalomyelitis followed by optic neuritis without anti-myelin oligodendrocyte glycoprotein antibodies: a biopsied case report.

BACKGROUND: Acute disseminated encephalomyelitis (ADEM) followed by optic neuritis (ADEM-ON) is characterized by the following features: early onset, monophasic or multiphasic ADEM followed by one or more episodes of ON, and the presence of serum anti-myelin oligodendrocyte glycoprotein (MOG) antibodies. CASE REPORT: We report a case of ADEM-ON without anti-MOG antibodies in a 78-year-old woman. The patient developed acute-onset neurological findings and was diagnosed with ADEM. She was treated with intravenous methylprednisolone (IVMP), and oral corticosteroids. Her clinical symptoms and MRI findings subsequently improved. Left optic neuritis emerged 6 months later, and we made a diagnosis of ADEM-ON. A brain biopsy performed during the acute phase of ADEM showed perivascular infiltration of macrophages with demyelination. CONCLUSION: The majority of the reported ADEM-ON cases are pediatric cases with serum anti-MOG antibodies, but our patient was the elderly, without anti-MOG antibodies. Moreover, the pathological features of our case were similar to those observed in patients with typical ADEM and in patients with anti-MOG antibody-positive ADEM. Although ADEM-ON is related to the presence of anti-MOG antibodies, factors other than anti-MOG antibodies could contribute to the development of ADEM-ON.

The effect of optic neuritis treatment trial (ONTT) combined corticosteroid regimen on pattern reversal visual evoked potentials: a prospective follow-up study.

BACKGROUND: The combined corticosteroid regimen of the original Optic Neuritis Treatment Trial (ONTT) is used in many centers to treat optic neuritis. Though pattern reversal visual evoked potentials (PRVEPs) are a sensitive, standard measure of visual conduction in optic neuritis, no studies hitherto have investigated the effect of combined ONTT regimen on PRVEPs. We aimed to determine the effect of combined corticosteroid regimen of the ONTT on changes of PRVEPs in patients with first-episode optic neuritis over 3 months post-treatment. METHODS: This is a prospective, observational study in which 44 patients with optic neuritis were seen pre-treatment (baseline) and follow-up, at 1 month (FU1) and 3 months (FU2). Twenty-nine patients were treated with ONTT combined regimen (ONTT+ Group) while 15 were conservatively managed without corticosteroids (ONTT- Group). The median latency and amplitude values of the P100 PRVEP component and the visual acuity (i.e. LogMAR values) at pre-treatment, FU1 and FU2 were compared in the two groups using Friedman's rank test and Wilcoxon Signed Ranks test. RESULTS: Median P100 latency improved significantly (to the normal range) as early as by 1 month after the commencement of treatment in the ONTT+ Group, and then remained significantly lower than the baseline over next 2 months. In the ONTT- Group, the median P100 latency improved more slowly over the two follow up assessments and reached the normal range by 3 months. Median visual acuity values also improved significantly at 1 and 3 months after the commencement of treatment in the ONTT+ Group but not in the ONTT- Group. CONCLUSION: ONTT combined corticosteroid regimen improves conduction in the visual pathways of patients with first-episode optic neuritis earlier than does conservative management. We provide electrodiagnostic evidence that combined ONTT regimen-compared with conservative management-results in early remission of visual conduction abnormalities in first-episode optic neuritis.

Optic neuritis of MOG-IgG-associated autoimmune disorders: a case report.

BACKGROUND: The diagnosis of immunoglobulin G serum antibodies to myelin oligodendrocyte glycoprotein (MOG-IgG) associated inflammatory demyelinating disorders can be confirmed by the presence of MOG-IgG, yet its general cut-off concentration had not yet to be defined. Whether it is significant that a seropositive lower titer level for MOG-IgG could cause disease is still unknown. CASE PRESENTATION: A 55-year-old Chinese woman presented with acute optic neuritis manifestations in the left eye. MRI showed a left optic nerve demyelination image and a T2 hyperintensity at C7 vertebral segment without any extra specific lesions. AQP4-IgG was tested seronegative, while the MOG-IgG was positive, titer 1:10, by indirect immunofluorescence. Considering the lower concentration, we retested serum MOG-IgG after 6 months of steroid therapy, using cell-based assay, then we still got the same result which was also barely above the negative cut-off value. So, the clinical diagnose was "possible MOG-IgG-associated encephalomyelitis". The woman's condition improved by steroid therapy without relapse. CONCLUSIONS: Seropositive MOG-IgG, even at a lower level, could lead to an autoimmune inflammatory demyelination. In adults, it commonly presents as ON and myelitis. Although the patient had a considerable reaction, steroid therapy could not make MOG-IgG seronegative, instead, the antibody may persist even during remission and flare-ups can recur after steroid withdrawal. Therefore, a long-term follow-up is necessary to monitor the patient's prognosis.

Clinical phenotype, radiological features, and treatment of myelin oligodendrocyte glycoprotein-immunoglobulin G (MOG-IgG) optic neuritis.

PURPOSE OF REVIEW: To review the clinical characteristics, radiological manifestations and treatment of myelin oligodendrocyte glycoprotein (MOG)-immunoglobulin G (IgG) optic neuritis. RECENT FINDINGS: Serum antibodies to MOG have recently been found to be a biomarker of MOG-IgG-associated disorder (MOGAD), a demyelinating disease distinct from both multiple sclerosis (MS) and aquaporin-4-IgG neuromyelitis optica spectrum disorder (AQP4-IgG-positive NMOSD). The phenotype of MOGAD is broad and includes optic neuritis, transverse myelitis, and acute demyelinating encephalomyelitis (ADEM). Optic neuritis is the most common presentation in adults, whereas ADEM is the most common presentation in children. Clinical characteristics suggestive of MOG-IgG optic neuritis include recurrent optic neuritis, prominent disc edema, and perineural enhancement of the optic nerve on magnetic resonance imaging. Although the nadir of vision loss is severe with MOG-IgG optic neuritis, the recovery is typically better than AQP4-IgG optic neuritis and therefore has a favorable overall prognosis. Patients with relapsing disease will often need chronic immunotherapy. Rituximab, azathioprine, mycophenolate mofetil, and monthly intravenous immune globulin are the most commonly utilized treatments. SUMMARY: MOGAD is a unique entity that is separate from both MS and AQP4-IgG-positive NMOSD. Recognition of the clinical and radiologic features allow for the correct diagnosis. Future randomized trials will determine the optimal treatment for MOGAD.