Trends in Plasma Exchange Use in Optic Neuritis Hospitalizations in the United States.

PURPOSE: To report use trends of plasma exchange (PLEX) as well as sociodemographic and medical comorbidities associated with PLEX in the United States. DESIGN: Retrospective cross-sectional study. PARTICIPANTS: Adult patients (≥ 18 years) admitted for inpatient hospitalization with a primary diagnosis of optic neuritis (ON). METHODS: Data from the National Inpatient Sample database was compiled to assess PLEX use rates between 2000 and 2020. The cohorts of patients receiving PLEX versus not receiving PLEX were analyzed between quarter 4 of 2015 through 2020 (International Classification of Diseases, Tenth Revision [ICD-10], only) for patient sociodemographic variables, medical diagnoses, insurance types, hospital characteristics, cause of disease, time to therapy, length of stay (LOS), and total charges incurred. MAIN OUTCOME MEASURES: Incidence of ON, incidence of PLEX, demographics, diagnoses associated with PLEX therapy, total charges, and LOS. RESULTS: From 2000 through 2020, 11 209 patients hospitalized with a primary diagnosis of ON were identified, with a significant majority managed at urban teaching hospitals. Use of PLEX increased steadily over 2 decades from 0.63% to 5.46%. Use was greatest in the western United States and least in the eastern United States. In the subset of ICD-10 cases, 3215 patients were identified. The median time to therapy of PLEX was 1 day after admission, and PLEX use was highest in patients with neuromyelitis optica spectrum disorder (NMOSD) (21.21%) and lowest in multiple sclerosis-associated ON (3.80%). Use of PLEX was associated with significantly longer LOS and higher total charges incurred. Medical comorbidities associated with PLEX included adverse reaction to glucocorticoids (adjusted odds ratio [aOR], 31.50), hemiplegia (aOR, 28.48), neuralgia (aOR, 4.81), optic atrophy (aOR, 3.74), paralytic strabismus (aOR, 2.36), and psoriasis (aOR, 1.76). CONCLUSIONS: Over the last 2 decades in the United States, PLEX therapy for ON has increased, with the highest use in the western United States and for patients with the diagnosis NMOSD ON. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Optic Neuritis and Cranial Neuropathies Diagnosis Rates before Coronavirus Disease 2019, in the Initial Pandemic Phase, and Post-Vaccine Introduction.

PURPOSE: To compare rates of diagnosis of neuro-ophthalmic conditions across the Coronavirus Disease 2019 (COVID-19) pandemic with pre-pandemic levels. DESIGN: Multicenter, retrospective, observational study. PARTICIPANTS: Patients seen for eye care between March 11, 2019, and December 31, 2021. METHODS: A multicenter electronic health record database, Sight Outcomes Research Collaborative (SOURCE), was queried for new diagnoses of neuro-ophthalmic conditions (cranial nerve [CN] III, IV, VI, and VII palsy; diplopia; and optic neuritis) and new diagnoses of other ophthalmic conditions from January 1, 2016, to December 31, 2021. Data were divided into 3 periods (pre-COVID, pre-COVID vaccine, and after introduction of COVID vaccine), with a 3-year look-back period. Logistic regressions were used to compare diagnosis rates across periods. Two-sample z-test was used to compare the log odds ratio (OR) of the diagnosis in each period with emergent ocular conditions: retinal detachment (RD) and acute angle-closure glaucoma (AACG). MAIN OUTCOME MEASURES: Diagnosis rate of neuro-ophthalmic conditions in each study period. RESULTS: A total of 323 261 unique patients (median age 59 years [interquartile range, 43-70], 58% female, 68% White) across 5 academic centers were included, with 180 009 patients seen in the pre-COVID period, 149 835 patients seen in the pre-COVID vaccine period, and 164 778 patients seen in the COVID vaccine period. Diagnosis rates of CN VII palsy, diplopia, glaucoma, and cataract decreased from the pre-COVID period to the pre-vaccine period. However, the optic neuritis diagnoses increased, in contrast to a decrease in RD diagnoses (P = 0.021). By comparing the diagnosis rates before and after widespread vaccination, all eye conditions evaluated were diagnosed at higher rates in the COVID vaccination period compared with pre-COVID and pre-vaccine periods. The log OR of neuro-ophthalmic diagnosis rates across every period comparison were largely similar to emergency conditions (RD and AACG, P > 0.05). However, the log OR of cataract and glaucoma diagnoses were different to RD or AACG (P < 0.05) in each period comparison. CONCLUSIONS: Neuro-ophthalmic diagnoses had a similar reduction in diagnosis rates as emergent eye conditions in the first part of the pandemic, except optic neuritis. After widespread COVID-19 vaccination, all ophthalmic diagnosis rates increased compared with pre-pandemic rates, and the increase in neuro-ophthalmic diagnosis rates did not exceed the increase in RD and AACG diagnosis rates. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

The Risk of Optic Neuritis following mRNA Coronavirus Disease 2019 Vaccination Compared to Coronavirus Disease 2019 Infection and Other Vaccinations.

PURPOSE: To determine the risk of optic neuritis (ON) after mRNA Coronavirus Disease 2019 (COVID-19) vaccine administration. DESIGN: U.S. National aggregate database retrospective cohort study. PARTICIPANTS: Patients were placed into cohorts based on mRNA COVID-19 vaccination status (no vaccine and positive history of COVID-19 infection, 1 vaccine, or 2 vaccines received) from December 2020 to June 2022. Two control cohorts were created with patients vaccinated against influenza or tetanus, diphtheria, and pertussis (Tdap) from June 2018 to December 2019. Patients with any history of ON or significant risk factors for ON development including infectious, inflammatory, and neoplastic diseases were excluded. METHODS: A large deidentified database was queried for the Common Procedural Technology codes for immunization encounters specific to first dose and second dose of mRNA COVID-19 vaccine, influenza, or Tdap. Cohorts were 1:1 propensity score matched on age, sex, race, and ethnicity. The risk of ON development after vaccination was calculated and compared for all 5 cohorts with 95% confidence intervals (CIs) reported. MAIN OUTCOME MEASURES: Risk ratio (RR) of ON 21 days after vaccination (or COVID-19 infection) and incidence of ON per 100 000 individuals. RESULTS: After matching, the first dose COVID-19 and influenza vaccine cohorts (n = 1 678 598, mean age [standard deviation] at vaccination of 45.5 [23.3] years and 43.2 [25.5] years, 55% female) the RR of developing ON was 0.44 (95% CI, 0.28-0.80). The first dose of COVID-19 and Tdap vaccinations (n = 797 538, mean age 38.9 [20.0] years, 54.2% female) cohort had 10 and 16 patients develop ON (RR, 0.63; 95% CI, 0.28-1.38). Comparison of COVID-19-vaccinated patients (n = 3 698 848, 48.2 [21.5] years, 54.7% female) to unvaccinated and COVID-19-infected patients (n = 3 698 848, 49.6 [22.0] years, 55.2% female) showed 49 and 506 patients developing ON, respectively (RR, 0.09; 95% CI, 0.07-0.12). The incidence per 100 000 for ON was 1 in the first dose COVID-19 vaccine cohort, 2 in the influenza cohort, and 2 in the Tdap cohort, and 14 in the COVID-19-infected and unvaccinated cohorts. CONCLUSIONS: Risk of ON after mRNA COVID-19 vaccination is rare and comparable to Tdap vaccination, decreased compared with influenza vaccination, and decreased compared with COVID-19 infection in the absence of vaccination. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

Risk of central nervous system demyelinating attack or optic neuritis recurrence after pediatric optic neuritis in Korea.

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.

Ocular Manifestations of Multiple Sclerosis: A Population-Based Study.

BACKGROUND: To evaluate the population-based frequency and severity of multiple sclerosis (MS)-related ocular diseases. METHODS: Retrospective, population-based study examining patients with MS between January 1, 1998 and December 31, 2011. Patients were identified using the Rochester Epidemiology Project, which is a record-linkage system of medical records for all patient-physician encounters among Olmsted County, Minnesota residents. Diagnosis of MS was confirmed based on neuroimaging, cerebrospinal fluid studies, and serum studies for each patient according to the 2017 McDonald criteria. Patient data were obtained using the medical records and followed through April 1, 2018. RESULTS: Of the 116 patients with MS, 66% were female and the median age of onset was 36 years (interquartile range 27.5-43.5 years). About half (61/116, 53%) had MS-related neuro-ophthalmic manifestations during their disease course, and about one-fourth (33/116, 28%) had visual symptoms as their presenting symptom of MS, most commonly as optic neuritis (26/116, 22%). Optic neuritis was the leading MS-related ocular condition (37%), followed by internuclear ophthalmoplegia (16%) and nystagmus (13%). Optic neuritis was mostly unilateral (40/43, 93%), with 16% (6/43) having a visual acuity of 20/200 or worse at nadir but ultimately 95% (35/37) improving to a visual acuity of 20/40 or better. CONCLUSIONS: This study provides the population-based frequency of MS-related ocular disease, which demonstrates a high frequency of ocular manifestations in MS both at disease onset and during the disease course, emphasizing the utility of neuro-ophthalmologists, or collaboration between neurologists and ophthalmologists, in the care of patients with MS.

Evaluation of demographic and neuro-ophthalmologic findings of patients with multiple sclerosis.

PURPOSE: The study aims to investigate the demographic and neuroophthalmologic features of patients with multiple sclerosis (MS). METHODS: This retrospective study investigated 270 eyes of 135 patients with MS. All subjects underwent a full ophthalmological examination. RESULTS: The study investigated 270 eyes of 135 patients with MS. The patients included 102 (74.8%) females and 34 (25.2%) males. The mean age at the time of diagnosis of MS was 29.9 ± 9.6 years. The mean follow-up period was 6.7 ± 10.9 months. Initial symptoms of MS at presentation included optic neuritis (ON) in 42 patients (15.6%), numbness of hands and feet in 20 patients (7.4%) and diplopia in 11 patients (4.1%). Additional diseases were observed in 29 patients (21.5%) and autoimmune diseases were observed in 11 patients (8.1%). Thirteen patients (9.62%) had relatives with MS; the relatives of five patients were first-degree relatives and the relatives of the remaining eight patients were second-degree relatives. Table 2 summarizes the additional systemic and ocular diseases and family history data. During MS, 72 patients (53.4%) were diagnosed with ON. ON was bilateral in 49 patients (68%) and unilateral in 23 patients (32%). Retrobulbar ON was observed in 77 eyes (81.6%) and papillitis was observed in 18 eyes (18.4%). Disorders of efferent visual pathway function were found in 43 patients (30.4%). CONCLUSION: Visual impairments are significant in patients with MS. Although ON is the most prevalent symptom of MS, it is important to keep in mind that damage to the efferent visual system can be observed.

Clinical outcomes of optic neuritis: A retrospective study at a tertiary medical center in Saudi Arabia.

OBJECTIVES: To investigate the clinical results of optic neuritis (ON) patients in a tertiary medical facility in Makkah, Kingdom of Saudi Arabia. METHODS: The data of patients assessed for ON at Makkah, Saudi Arabia's King Abdullah Medical Center (KAMC), was examined retrospectively. RESULTS: We identified 15 patients with ON. The ON was caused by multiple sclerosis (MS) in 73.3% of patients and neuromyelitis optica spectrum disorder (NMOSD) in 26.7% of patients. The disease was bilateral in 60% of patients and unilateral in 40% of patients. Additionally, 60% of patients had 2 or more episodes of ON, whereas 40% had a single episode. Patients with ON who presented with painful eye movements had a significantly longer disease duration (p=0.032). Moreover, patients whose disease duration was 11-15 days did not achieve a complete resolution of their symptoms and experienced some residual vision loss compared to 30.8% who had continued visual changes (p=0.049). CONCLUSION: In the studied population, multiple sclerosis was the most prevalent cause of ON. Women were more likely to have ON. The prognosis for eyesight was substantially connected with the length of ON.

Clinical Profile and Outcome of Pediatric Demyelinating Disorders in Calabar, Nigeria: A Case Series.

BACKGROUND: Demyelinating disorders of the central nervous system (CNS) are rare disorders characterized by inflammation and the selective destruction of CNS myelin. The incidence of this disorder is increasing in developed countries. Nigerian studies on the pediatric population on the subject are very scarce. AIMS: The aim of the study was to document the epidemiology, clinical profile, and impact of late presentation on the treatment outcome of demyelinating diseases of the CNS in pediatric patients. METHODS: The retrospective review of patients aged 1-15 years admitted in a tertiary hospital from January 2018 to December 2022 with various symptoms suggestive of demyelinating CNS disorders. The diagnosis was clinically and radiologically confirmed. Information retrieved from the case notes included patients' demographics, clinical symptoms and signs, number of days with symptoms to presentation in the hospital, results of the magnetic resonance imaging (MRI), treatment, and treatment outcomes. Data were entered in Excel sheet and results were presented in tables and percentages. RESULTS: The incidence of demyelinating disorders over the period was 0.013% (10 out of 769 patients admitted over the period). Acute demyelinating encephalomyelitis (ADEM) was the most common disorder seen in the study population (60%, n = 6), followed by transverse myelitis and two (20%) had optic neuritis (ON). Most of the patients with ADEM were in the 1-5-year age group. The female-to-male ratio was 2.3:1. Paraplegia, visual impairment, and ataxia were the most common clinical presentations in the study population. One of the patients met the criteria for the diagnosis of multiple sclerosis during follow-up. Human immunodeficiency virus (HIV) was identified as the cause of demyelination in one case. Most of the patients improved with steroids. CONCLUSION: ADEM was the most common clinical phenotype seen in this study. Patients with ADEM and ON had a better prognosis than transverse myelitis. Late presentation was also identified as a poor prognostic factor. Follow-up of cases is very important to monitor disease progression to multiple sclerosis.

Epidemiological and clinical characteristics of myelin oligodendrocyte glycoprotein antibody-associated disease in a nationwide survey.

BACKGROUND: To our knowledge, no nationwide epidemiological study of myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) has been conducted. OBJECTIVE: We examined the epidemiology and clinical features of MOGAD in Japan. METHODS: We distributed questionnaires on the clinical characteristics of patients with MOGAD to neurology, pediatric-neurology, and neuro-ophthalmology facilities throughout Japan. RESULTS: In total, 887 patients were identified. The estimated number of total and newly diagnosed MOGAD patients was 1,695 [95% confidence interval (CI): 1483-1907] and 487 (95% CI: 414-560), respectively. The estimated prevalence and incidence were 1.34/100,000 (95% CI: 1.18-1.51) and 0.39/100,000 (95% CI: 0.32-0.44), respectively. The median age at onset was 28 years (range: 0-84 years). At onset, optic neuritis was present in approximately 40% of patients, irrespective of the onset age. Acute disseminated encephalomyelitis was more frequent in younger patients, whereas brainstem encephalitis, encephalitis, and myelitis were more frequent in elderly patients. Immunotherapy was highly effective. CONCLUSION: The prevalence and incidence rates of MOGAD in Japan are similar to those in other countries. Notable characteristics such as the preferential occurrence of acute disseminated encephalomyelitis in children exist; however, general characteristics including symptoms and treatment response are common irrespective of the onset age.

Development of a Prognostic Model for Predicting Multiple Sclerosis After Optic Neuritis: A Secondary Analysis of Data From the Optic Neuritis Treatment Trial.

BACKGROUND: Optic neuritis can be the initial manifestation of multiple sclerosis (MS). The purpose of this study was to develop a prognostic model for predicting the risk of MS development among patients with optic neuritis. METHODS: The data from 388 patients with optic neuritis were retrieved from the Optic Neuritis Treatment Trial (ONTT). Cox proportional hazards regression analysis was used to develop a prognostic model. The performance of the model was assessed by using Harrell's C-index and calibration curves. The rates of MS development were estimated using the Kaplan-Meier method. RESULTS: Among the enrolled subjects, a total of 154 (39.7%) patients developed clinically definite MS during a median follow-up period of 15.8 years (interquartile range, 7.2-16.9 years). The factors associated with the development of MS were the presence of brain lesions as on baseline MRI, previous nonspecific neurologic symptoms, commencing low-dose corticosteroids treatment, ocular pain, and absence of optic disc/peripapillary hemorrhage. After incorporating these 5 factors into the prognostic model, a C-index of 0.72 (95% confidence interval [CI], 0.69-0.76) and good calibration curves were obtained. The C-index of the model was significantly higher than the C-indexes of any single factor (P < 0.001 in all cases). The model was able to stratify the ONTT patient cohort into 3 risk groups with significantly different intergroup rates of developing MS (rates for developing MS within a 15-year period: high-risk group, 75.7% [95% CI, 65.6%-82.9%], intermediate-risk group, 44.7% [95% CI, 31.4%-55.4%]; and low-risk group, 20.8% [95% CI, 14.2%-26.8%]; log-rank P < 0.001). CONCLUSIONS: This prognostic model had a better prediction ability when compared with the standard practice that relies solely on using brain lesions on MRI. It can, therefore, help guide decision-making to initiate earlier disease-modifying therapy for patients with optic neuritis at risk of developing MS.

Cognitive Performance of Patients With Multiple Sclerosis and Optic Neuritis at Presentation.

BACKGROUND: Cognitive dysfunction is common among patients with multiple sclerosis (MS), but the effect of coexisting optic neuritis (ON) at the first presentation of multiple sclerosis on the course of cognitive decline is unknown. The purpose of this study was to assess whether ON at presentation has any effect on the progression of cognitive decline in MS. METHODS: Historical cohort study. We retrospectively compared the cognitive performance of patients with relapsing-remitting MS with and without ON at the time of MS diagnosis. Subjects were included if cognitive test results were available both at baseline and after at least 36 months from presentation and grouped based on the presence (MS-ON) or absence (MS-non-ON) of optic neuritis at presentation. RESULTS: One hundred seventy consecutive subjects with MS were found suitable, with a 1:2 male:female ratio and a mean age at diagnosis of 33.0 ± 10.9 years. Forty-six patients (27.1%) presented with ON. No significant differences were found in cognitive performance at onset between the 2 groups. Both groups had a similar follow-up duration. The prevalence of cognitive decline in the general score was significantly higher in the MS-ON group compared with the MS-non-ON group (6.5% vs 0%, respectively; P < 0.001), as well as in the attention (8.7% vs 1.6%; P = 0.046) and the executive function (17.4% vs 2.4%; P = 0.001) domains. CONCLUSIONS: Optic neuritis at presentation of MS is associated with a higher prevalence of cognitive decline over time. Potential benefit of early intervention to prevent cognitive decline may be warranted.

Advances in ophthalmic structural and functional measures in multiple sclerosis: do the potential ocular biomarkers meet the unmet needs?

PURPOSE OF REVIEW: Multiple sclerosis is a heterogeneous disorder. Biomarkers to monitor disease activities are highly desirable especially because of the recent shift toward personalized medicine that coincides with the expansion of disease-modifying therapy. The visual system is highly involved in multiple sclerosis, and the rapid advancement of ophthalmic techniques has boosted the development of potential ocular biomarkers for multiple sclerosis management. RECENT FINDINGS: Recent studies have found that the rapid thinning of the peripapillary retinal nerve fiber layer and ganglion cell-inner plexiform layer (GCIPL) occurs in the progressive stage. Furthermore, the inter-eye thickness difference of the GCIPL could be used in identifying unilateral optic neuritis to facilitate the early diagnosis of multiple sclerosis. Moreover, the retinal microvascular alterations measured as vessel density were found to be related to the disability and visual function, although a standardized protocol to measure retinal microvascular alterations has not been well established. Additionally, aberrant ocular motility, such as fixation microsaccades, can be used to measure disability objectively. SUMMARY: The fast expansion of potential ocular biomarkers measured as retinal microstructural, microvascular, and ocular motility changes may facilitate the diagnosis and management of multiple sclerosis.

"NMDA receptor spectrum disorder" in the differential diagnosis of demyelinating disorders of the CNS: optic neuritis and myelitis.

OBJECTIVE: The aim of this study was to investigate the frequency of anti-N-methyl-D-aspartate receptor (anti-NMDAR) antibody positivity in patients presenting with transverse myelitis (TM) and/or optic neuritis (ON), to describe their neurologic and radiological characteristics, and to compare these characteristics with those reported in previous studies. MATERIAL AND METHODS: This study included 179 patients (ON: 96, TM: 74, ON and TM: 9) who visited Isfahan Multiple Sclerosis Center from January 2017 to September 2019, for approximately 32 months. The respective neurological examinations were performed. Demographic data of the patients, as well as findings from radiological and serological investigations were obtained. RESULTS: Frequencies of anti-NMDAR seropositivity in patients with TM, ON, and concurrent TM and ON were approximately 3.4%, 1.4%, and 11.1%, respectively. None exhibited any psychiatric symptoms. CONCLUSION: Based on the frequency of seropositivity for anti-NMDAR antibody in our patients, positivity for this antibody appears to be more frequent than previously anticipated in patients presenting with these conditions. We recommend that the anti-NMDAR antibody presence in CSF/serum be checked and considered in addition to the routine examinations performed upon confronting demyelinating conditions such as TM and ON. We suggest considering the term "NMDAR spectrum disorder" to more clearly distinguish the potentially overlapping conditions with different etiologies in patients with CNS disorders.

Population-based Incidence of Pediatric and Adult Optic Neuritis and the Risk of Multiple Sclerosis.

PURPOSE: To determine the age- and sex-specific prevalence and incidence of demyelinating optic neuritis and the risk of multiple sclerosis (MS) in pediatric and adult populations in South Korea. DESIGN: A nationwide, population-based, retrospective study using data from the Korean National Health Claims database from 2010 to 2016. PARTICIPANTS: The entire South Korean population aged 65 years of age or younger (n = 44 700 564). All patients with optic neuritis from the entire Korean population were included. METHODS: Patients aged 14 years of age or younger were classified as pediatric patients, and those aged 15 to 65 years were classified as adults. Each group was analyzed separately. Patients with optic neuritis had a subsequent diagnosis, including idiopathic, MS, neuromyelitis optica (NMO), and acute disseminated encephalomyelitis. Prevalence and incidence, conversion rate to MS, and treatment modalities (steroids, plasmapheresis, interferon-ß, and immunosuppressants) were estimated. MAIN OUTCOME MEASURES: Prevalence and incidence of optic neuritis, and conversion rate to MS. RESULTS: Among 44 700 564 individuals, 531 pediatric patients (50.7% female) and 7183 adults (53.3% female) were identified as having optic neuritis. Annual incidence was 1.04 (95% confidence interval [CI], 1.01-1.07) per 100 000 pediatric individuals and 3.29 (95% CI, 3.28-3.30) per 100 000 adults. Peak incidence was observed at 10 to 14 years in the pediatric population and at 30 to 34 years and 50 to 54 years in the adult population. Conversion rate to MS was 13.8% in the pediatric population and 11.4% in the adult population. Fourteen percent of all patients were treated with chronic immunosuppressants, 38% of patients with NMO underwent plasmapheresis, and 50% of patients with MS were treated with interferon-ß. CONCLUSIONS: This is a nationwide epidemiologic study of optic neuritis in individuals of all ages in South Korea. The incidence of optic neuritis and subsequent risk of MS in the pediatric population are comparable to those reported in western countries but are lower in the adult population than in western countries. The incidence rate in adults was 3.2-fold higher than in the pediatric population, and the overall MS conversion rate in the entire Korean population was estimated to be 10.6%.

The clinical spectrum and incidence of anti-MOG-associated acquired demyelinating syndromes in children and adults.

OBJECTIVES: The aim of this study was to assess the Dutch nationwide incidence of myelin oligodendrocyte glycoprotein (MOG)-IgG-associated acquired demyelinating syndromes (ADS) and to describe the clinical and serological characteristics of these patients. METHODS: All serum samples for routine diagnostics from February 2014 to December 2017 were sent to the single central reference laboratory for the full-length MOG-IgG cell-based assay (CBA) in the Netherlands. Clinical data from patients known in our National ADS centre were available. RESULTS: A total of 1414 samples of 1277 patients were received; of these, 92 patients (7%) were MOG-IgG-seropositive. The mean incidence was 0.16/100,000 people, with higher seropositivity in children (0.31/100,000) than in adults (0.13/100,000). In MOG-IgG-positive patients at the National ADS centre (61/92, 66%), the most common presenting phenotype is acute disseminated encephalomyelitis (ADEM, 56%) in children and optic neuritis (ON, 44%) in adults. Relapsing disease occurred in 9/34 (26%) children and 11/27 (41%) adults during median follow-up of 27.5 months. Patients were tested MOG-IgG-positive >200 months after the initial attack, suggesting an extended time to first relapse (TTFR). Longitudinal analysis of MOG-IgG (25/61, 41%) showed that 67% of the monophasic patients remain seropositive and 60% in relapsing patients. Majority of seronegative patients had no relapses (89%). CONCLUSION: This nationwide study shows that the overall incidence of MOG-IgG-seropositive disorders is 0.16 per 100,000 people. The distribution over the clinical phenotypes differs between adults and children. Seropositivity can be maintained over years even without clinical activity, while seronegative patients generally had no relapses.

Optic neuritis in German children: clinical findings and association with multiple sclerosis.

PURPOSE: Analysis of a cohort of pediatric optic neuritis patients concerning the epidemiology, disease progression, and association with multiple sclerosis (MS). METHODS: Retrospective, observational cohort study. From 2004 to 2018, all electronic medical files of patients younger than 18 years referred to a tertiary care clinic in Germany with the diagnosis optic neuritis have been analyzed. RESULTS: Sixty-nine patients were referred in the study period, 16 did not suffer under optic neuritis and were excluded. The median visual acuity of the remaining 53 patients was 0.07 at the baseline examination and 1.0 at the latest follow-up examination (decimal notation, median 2.1 years after baseline). Forty-two percent of the patients developed MS during the study period. Female sex (p = 0.028) as well as higher age (p = 0.0082) proved to be statistically significant risk factors for MS development. CONCLUSION: The prognosis for restoring vision in pediatric optic neuritis was favorable. During the observation period, the risk of developing MS was overall 42% and 8% for patients younger than 11 years. The percentage of MS as underlying cause of optic neuritis does not differ remarkably between children older 10 years and adults.

Conversion of Optic Neuritis to Relapsing Remitting Multiple Sclerosis: A Retrospective Comorbidity Cohort Study.

OBJECTIVE: The aim of the study was to determine the risk of multiple sclerosis (MS) conversion after optic neuritis (ON) and to identify the predictive factors on conversion in Turkish patients. METHODS: Patients whose first clinical attacks had been ON were included in the study. The primary end point was the diagnosis of clinical relapse-remitting MS. RESULT: Except for the bilateral involvement rate, the clinical and demographic characteristics of the cohort are similar to Western studies. Though one-third of the patients with ON had bilateral involvement, bilateral involvement reduces the risk of conversion. Also, active lesions at the initial cranial magnetic resonance imagination increase the conversion rate. CONCLUSION: This research confirms previous findings and contributes additional evidence that if the patients have unilateral involvement and active lesions, they should be closely monitored. Moreover, our research supports the hypothesis that risk factors may be affected by racial, environmental, and genetic factors.

Neuromyelitis optica spectrum disorders in South of Tunisia: A rare entity with low seroprevalence of anti-aquaporin 4 autoantibodies.

INTRODUCTION: Screening for anti-aquaporin 4 (anti-AQP4) antibodies, a specific marker of neuromyelitis optica spectrum disorders (NMOSD), is part of the immunological investigation performed in a context of central nervous system (CNS) inflammation with optic neuritis and/or myelitis. The aim of our study was to evaluate the prevalence and the diagnostic value of anti-AQP4 antibodies in Tunisian patients with such inflammatory neurological conditions. METHODS: During 3years, 170 consecutive serum samples of Tunisian patients with CNS inflammatory disorders and optico-spinal involvement were tested in our laboratory for anti-AQP4 antibodies using indirect immunofluorescence on transfected cells. RESULTS: The global seroprevalence of anti-AQP4 in our study was 4.1% (7 cases/170). The diagnosis of NMOSD was made for the 7 seropositive patients and for 2 seronegative patients, which leads to a seroprevalence of 77.7% in our NMOSD subgroup. The detection of anti-AQP4 allowed the diagnosis of NMOSD in 4 patients with incomplete clinical presentation and 5 patients with positive antinuclear antibodies. In one case, seropositivity was detected in a second sample, one year after an initial seronegativity. CONCLUSION: NMOSD seem to represent a rare etiology of optic neuritis and/or myelitis in Tunisian patients. Despite its low global seroprevalence in our study population, anti-AQP4 appears to be a very clinically relevant marker for NMOSD diagnosis. Repeating the screening in case of initial negativity could be interesting in clinical practice.

Epidemiologic and Clinical Characteristics of Optic Neuritis in Japan.

PURPOSE: To elucidate the clinical and epidemiologic characteristics of optic neuritis in Japan. DESIGN: Multicenter cross-sectional, observational cohort study. PARTICIPANTS: A total of 531 cases of unilateral or bilateral noninfectious optic neuritis identified in 33 institutions nationwide in Japan. METHODS: Serum samples from patients with optic neuritis were tested for anti-aquaporin-4 antibodies (AQP4-Abs) and anti-myelin oligodendrocyte glycoprotein antibodies (MOG-Abs) using a cell-based assay and were correlated with the clinical findings. MAIN OUTCOME MEASURES: Antibody positivity, clinical and radiologic characteristics, and visual outcome. RESULTS: Among 531 cases of optic neuritis, 12% were AQP4-Ab positive, 10% were MOG-Ab positive, 77% were negative for both antibodies (double-negative), and 1 case was positive for both antibodies. Pretreatment visual acuity (VA) worsened to more than a median 1.0 logarithm of the minimum angle of resolution (logMAR) in all groups. After steroid pulse therapy (combined with plasmapheresis in 32% of patients in AQP4-Ab-positive group), median VA improved to 0.4 logMAR in the AQP4-Ab-positive group, 0 logMAR in the MOG-Ab-positive group, and 0.1 logMAR in the double-negative group. The AQP4-Ab-positive group showed a high proportion of females, exhibited diverse visual field abnormalities, and demonstrated concurrent spinal cord lesions on magnetic resonance imaging (MRI) in 22% of the patients. In the MOG-Ab-positive group, although posttreatment visual outcome was good, the rates of optic disc swelling and pain with eye movement were significantly higher than those in the AQP4-Ab-positive and double-negative groups. However, most cases showed isolated optic neuritis lesions on MRI. In the double-negative group, 4% of the patients had multiple sclerosis. Multivariate logistic regression analysis of all participants identified age and presence of antibodies (MOG-Ab and AQP4-Ab) as significant factors affecting visual outcome. CONCLUSIONS: The present large-scale cohort study revealed the clinicoepidemiologic features of noninfectious optic neuritis in Japan. Anti-aquaporin-4 antibody-positive optic neuritis has poor visual outcome. In contrast, MOG-Ab positive cases manifested severe clinical findings of optic neuritis before treatment, but few showed concurrent lesions in sites other than the optic nerve and generally showed good treatment response with favorable visual outcome. These findings indicate that autoantibody measurement is useful for prompt diagnosis and proper management of optic neuritis that tends to become refractory.