Espectro de neuromielitis óptica: ¿seropositivo para la anticuaporina es una entidad diferente de los pacientes que son seronegativos? Una perspectiva de Colombia / Neuromyelitis optica spectrum disorder: Do patients positive and negative for anti–aquaporin-4 antibodies present distinct entities? A Colombian perspective

Introducción: La neuromielitis óptica es una enfermedad inflamatoria del sistema nervioso central, caracterizada por ataques de neuritis óptica y mielitis transversa longitudinalmente extensa. El descubrimiento del biomarcador diagnóstico anticuerpo anti-acuaporina-4 y los hallazgos imagenológicos en resonancia magnética cerebral han permitido el reconocimiento de un fenotipo clínico más amplio y detallado denominado espectro neuromielitis óptica. Objetivo: Determinar las características demográficas y clínicas de los pacientes diagnosticados con NMO/NMOSD, de acuerdo con la seropositividad del anticuerpo, en dos instituciones de cuarto nivel de complejidad en Bogotá. Métodos: Se realizó un estudio tipo serie de casos. Fueron incluidos aquellos pacientes > 18 años con diagnóstico de NMO/NMOSD, valorados en el Servicio de Neurología de dos hospitales de alta complejidad entre los años 2013 y 2017, con disponibilidad de estudios imagenológicos y resultados de serología. Se evaluaron variables demográficas, clínicas e imagenológicas, y se realizó un análisis de estas variables, según seropositividad del Ac-AQP4. Resultados: Se incluyeron 35 pacientes con NMO/NMOSD, la mediana de edad de inicio fue de 46,5 años (P25-P75 = 34,2-54,0), la mayoría de los pacientes tuvo manifestaciones clínicas a nivel sensitivo (n = 25) y motor (n = 26), en seis (n = 6) pacientes se identificó una enfermedad autoinmune concomitante. Se encontró seropositividad en 20 pacientes. Encontramos algunas diferencias en las características clínicas e imagenológicas, pero solo la edad y el compromiso de nervio óptico mostraron diferencia estadísticamente significativa (p = 0,03). Conclusiones: No se encontraron grandes diferencias clínicas, imagenológicas y de laboratorio, según la seropositividad del Ac-AQP4, excepto en la edad de inicio y el compromiso de nervio óptico (uni o bilateral), pero deben ser estudiadas de manera más detallada en poblaciones más amplias.(AU)

Introduction: Neuromyelitis optica (NMO) is an inflammatory disease of the central nervous system characterised by attacks of optic neuritis and longitudinally extensive transverse myelitis. The discovery of anti–aquaporin-4 (anti-AQP4) antibodies and specific brain MRI findings as diagnostic biomarkers have enabled the recognition of a broader and more detailed clinical phenotype, known as neuromyelitis optica spectrum disorder (NMOSD). Objective: This study aimed to determine the demographic and clinical characteristics of patients with NMO/NMOSD with and without seropositivity for anti-AQP4 antibodies, in 2 quaternary-level hospitals in Bogotá. Methods: Our study included patients > 18 years of age and diagnosed with NMO/NMOSD and for whom imaging and serology results were available, assessed between 2013 and 2017 at the neurology departments of hospitals providing highly complex care. Demographic, clinical, and imaging data were gathered and compared in patients with and without seropositivity for anti-AQP4 antibodies. Results: The sample included 35 patients with NMO/NMOSD; the median age of onset was 46.5 years (P25-P75, 34.2-54.0); most patients had sensory (n = 25) and motor manifestations (n = 26), and a concomitant autoimmune disease was identified in 6. Twenty patients were seropositive for anti-AQP4 antibodies. Only age and presence of optic nerve involvement showed statistically significant differences between groups (p = .03). Conclusions: Clinical, imaging, and laboratory variables showed no major differences between patients with and without anti-AQP4 antibodies, with the exception of age of onset and presence of optic nerve involvement (uni- or bilateral); these factors should be studied in greater detail in larger populations.(AU)

Astrocytic outer retinal layer thinning is not a feature in AQP4-IgG seropositive neuromyelitis optica spectrum disorders.

BACKGROUND: Patients with anti-aquaporin-4 antibody seropositive (AQP4-IgG+) neuromyelitis optica spectrum disorders (NMOSDs) frequently suffer from optic neuritis (ON) leading to severe retinal neuroaxonal damage. Further, the relationship of this retinal damage to a primary astrocytopathy in NMOSD is uncertain. Primary astrocytopathy has been suggested to cause ON-independent retinal damage and contribute to changes particularly in the outer plexiform layer (OPL) and outer nuclear layer (ONL), as reported in some earlier studies. However, these were limited in their sample size and contradictory as to the localisation. This study assesses outer retinal layer changes using optical coherence tomography (OCT) in a multicentre cross-sectional cohort. METHOD: 197 patients who were AQP4-IgG+ and 32 myelin-oligodendrocyte-glycoprotein antibody seropositive (MOG-IgG+) patients were enrolled in this study along with 75 healthy controls. Participants underwent neurological examination and OCT with central postprocessing conducted at a single site. RESULTS: No significant thinning of OPL (25.02±2.03 µm) or ONL (61.63±7.04 µm) were observed in patients who were AQP4-IgG+ compared with patients who were MOG-IgG+ with comparable neuroaxonal damage (OPL: 25.10±2.00 µm; ONL: 64.71±7.87 µm) or healthy controls (OPL: 24.58±1.64 µm; ONL: 63.59±5.78 µm). Eyes of patients who were AQP4-IgG+ (19.84±5.09 µm, p=0.027) and MOG-IgG+ (19.82±4.78 µm, p=0.004) with a history of ON showed parafoveal OPL thinning compared with healthy controls (20.99±5.14 µm); this was not observed elsewhere. CONCLUSION: The results suggest that outer retinal layer loss is not a consistent component of retinal astrocytic damage in AQP4-IgG+ NMOSD. Longitudinal studies are necessary to determine if OPL and ONL are damaged in late disease due to retrograde trans-synaptic axonal degeneration and whether outer retinal dysfunction occurs despite any measurable structural correlates.

Frequency of New Silent MRI Lesions in Myelin Oligodendrocyte Glycoprotein Antibody Disease and Aquaporin-4 Antibody Neuromyelitis Optica Spectrum Disorder.

Importance: In multiple sclerosis, magnetic resonance imaging (MRI) new silent lesions contribute to the diagnostic criteria, have prognostic value, and are used in treatment monitoring; but in aquaporin-4 antibody neuromyelitis optica spectrum disorder (AQP4-NMOSD), they are rare between attacks. Their frequency and their association with relapses in adults with myelin oligodendrocyte glycoprotein antibody disease (MOGAD) are still unclear. Objective: To examine the frequency and characteristics of MRI new silent lesions in MOGAD and AQP4-NMOSD. Design, Setting, and Participants: This retrospective cohort study analyzed clinical and MRI data of 404 patients with MOGAD or AQP4-NMOSD between February 1, 1994, and April 1, 2021; data were prospectively recorded on the Oxford NMOSD clinical database under follow-up. The study was conducted at the Oxford National Referral Center for NMOSD. Participants included patients with MOGAD and AQP4-NMOSD who were treated within the Oxford National NMO Specialist Service. Exposures: Seropositive MOGAD and AQP4-NMOSD patients who had MRIs during attacks and the remission phase of their disease. Main Outcomes and Measures: Frequency of new silent lesions detected by either attack MRIs (during the acute clinical event) or remission MRIs (performed outside of a relapse and at least 3 months from last attack). Median time to next relapse in the presence of definite (reference MRI performed at least 4 weeks from last attack onset), probable (reference MRI performed during last attack), and no new silent lesions on remission MRIs was also evaluated. Results: One hundred eighty-two MOGAD patients and 222 AQP4-NMOSD patients were included. Of the MOGAD patients, 113 (62%) were female, median age at onset was 28 years (range, 2-72), and median follow-up was 52 months (range, 11-253). Of the AQP4-NMOSD patients, 189 (85%) were female, median age at onset was 43 years (range, 2-82), and median follow-up was 87.5 months (range, 11-260). MOGAD patients had 296 attack MRI sessions and 167 remission MRI sessions. New attack silent lesions were found in 97 of 296 (33%) attack MRI sessions, whereas new remission silent lesions were found in 5 of 167 (3.0%) remission MRI sessions. Median time from remission scan to the next relapse in the presence of definite or probable new remission lesions was 2 months (IQR, 1-6), whereas in the absence of any new remission lesions it was 73 months (IQR, 20-104; hazard ratio, 23.86; 95% CI, 7.51-75.79; P < .001). AQP4-NMOSD patients had 470 attack MRI sessions and 269 remission MRI sessions. New attack silent lesions were detected in 88 of 470 (18.7%) attack MRI sessions, whereas new remission silent lesions were found in 7 of 269 (2.6%) remission MRI sessions. Median time from remission scan to the next relapse in the presence of definite or probable new remission lesions was 5 months (IQR, 2-6), whereas in the absence of any new remission lesions it was 85 months (IQR, 29-167; hazard ratio, 21.23; 95% CI, 8.05-53.65; P < .001). Conclusions and Relevance: In contrast to that reported in multiple sclerosis, results of this cohort study suggest that new remission silent lesions are rare on follow-up scans in MOGAD and AQP4-NMOSD and appear to indicate a high risk of imminent relapse.

Early Initiation of Tocilizumab Treatment Against Moderate-to-Severe Myelitis in Neuromyelitis Optica Spectrum Disorder.

Background: Interleukin-6 receptor blockade is effective in reducing the risk of relapses in neuromyelitis optica spectrum disorder (NMOSD). However, its efficacy during acute attacks of NMOSD remains elusive. Objective: We investigated the effects of tocilizumab on disability during acute attacks, as well as its maintenance, in patients with moderate-to-severe myelitis. Methods: Nineteen patients with NMOSD received tocilizumab treatment as add-on to high-dose methylprednisolone (HDMP) in acute myelitis and twenty-two patients who only received HDMP were compared. Disease disability was assessed using a multi-level scaling system that included the expanded disability status scale (EDSS), Hauser ambulation index (HAI), modified Rankin scale (mRS), pain numerical rating scale (NRS), functional assessment of chronic illness therapy-fatigue scale (FACIT-F), activity of daily living (ADL), EuroQol five-dimensions-three-level questionnaire (EQ-5D-3L), and sensory function score and bowel and bladder function score in Kurtzke functional systems scores (FSS). Results: Improved EDSS, HAI, and mRS, as well as increased ADL and EQ-5D-3L were significant in patients on tocilizumab compared with those on steroids as monotherapy at 3 months (p < 0.05). Both groups of patients showed improved pain, fatigue, sensory function, and autonomic function at follow-ups, compared with baseline respectively. The changes in NRS, FACIT-F, and sensory and autonomic FSS showed no significant differences between the two groups. Tocilizumab significantly lowered the risk of relapses (HR = 0.21, 95% CI 0.06-0.76, p = 0.017) and reduced the annualized relapse rate compared with those by steroids (0.1 ± 0.2 vs 0.5 ± 0.6, p = 0.013). Conclusion: Early initiation of tocilizumab provided a safe and effective add-on alternative during attacks, and its maintenance contributed to a significant reduction of relapse rate in NMOSD.

Neuromyelitis Optica Spectrum Disorders in Africa: A Systematic Review.

BACKGROUND AND OBJECTIVES: Neuromyelitis optica (NMO) is a CNS inflammatory disease that predominantly affects the optic nerves and the spinal cord. It is more frequent in Asian and African populations than in European ones. Data on epidemiology, clinical presentation, additional investigations, and treatment in the African continent are scarce. We aim to (1) collect and analyze published data on neuromyelitis optica spectrum disorder (NMOSD), (2) indicate challenges in the diagnosis and management, and (3) discuss opportunities for future research, education, and policy making, specifically on the African continent. METHODS: A systematic review was performed in January 2021 with the search terms "Neuromyelitis optica and Africa," "Devic Disease and Africa," and "NMOSD and Africa." We included all study types except case reports, correspondence, or conference abstracts on NMO or NMOSD. Extracted data included study design, country, study period, demographic and clinical characteristics, results of paraclinical investigations, and outcome. Data analysis was performed with descriptive statistics. RESULTS: We retrieved a total of 79 records, of which 19 were included. Ten of 54 African countries reported a total of 410 cases. Almost half of them were from North African countries. The mean age at diagnosis was 33 years (range 7-88 years), and 75% were female. Transverse myelitis followed by optic neuritis were the most frequent symptoms at the time of presentation. One hundred nineteen patients experienced at least 1 previous relapse, and 106 had a relapsing course after diagnosis. Relapses were treated with IV methylprednisolone. Azathioprine and steroids were used most often as maintenance treatments. Outcomes were rarely described. DISCUSSION: The majority of studies on NMOSD from the African continent are retrospective, and most countries do not report any data. Our systemic review shows that data derived from patients living in Africa correspond well to what has been previously published in meta-analyses on patients of African ancestry with NMOSD who live outside of Africa, except for a younger age at onset and a lower proportion of females. We advocate for systematic data collection to adequately capture and monitor the burden of NMOSD, for expansion of research efforts and facilities to perform fundamental and clinical research, and for improved access to health care including diagnostics, treatments, and rehabilitation services for people affected by NMOSD in the African continent.

Clinical Features of COVID-19 on Patients With Neuromyelitis Optica Spectrum Disorders.

BACKGROUND AND OBJECTIVES: To describe the clinical features and disease outcomes of coronavirus disease 2019 (COVID-19) in patients with neuromyelitis optica spectrum disorder (NMOSD). METHODS: The Neuroimmunology Brazilian Study Group has set up the report of severe acute respiratory syndrome (SARS-CoV2) cases in patients with NMOSD (pwNMOSD) using a designed web-based case report form. All neuroimmunology outpatient centers and individual neurologists were invited to register their patients across the country. Data collected between March 19 and July 25, 2020, were uploaded at the REDONE.br platform. Inclusion criteria were as follows: (1) NMOSD diagnosis according to the 2015 International Panel Criteria and (2) confirmed SARS-CoV2 infection (reverse transcription-polymerase chain reaction or serology) or clinical suspicion of COVID-19, diagnosed according to Center for Disease Control / Council of State and Territorial Epidemiologists (CDC/CSTE) case definition. Demographic and NMOSD-related clinical data, comorbidities, disease-modifying therapy (DMT), COVID-19 clinical features, and severity were described. RESULTS: Among the 2,061 pwNMOSD followed up by Brazilian neurologists involved on the registry of COVID-19 in pwNMOSD at the REDONE.br platform, 34 patients (29 women) aged 37 years (range 8-77), with disease onset at 31 years (range 4-69) and disease duration of 6 years (range 0.2-20.5), developed COVID-19 (18 confirmed and 16 probable cases). Most patients exhibited mild disease, being treated at home (77%); 4 patients required admission at intensive care units (severe cases); and 1 patient died. Five of 34 (15%) presented neurologic manifestations (relapse or pseudoexacerbation) during or after SARS-CoV2 infection. DISCUSSION: Most NMOSD patients with COVID-19 presented mild disease forms. However, pwNMOSD had much higher odds of hospitalization and intensive care unit admission comparing with the general Brazilian population. The frequency of death was not clearly different. NMOSD disability, DMT type, and comorbidities were not associated with COVID-19 outcome. SARS-CoV2 infection was demonstrated as a risk factor for NMOSD relapses. Collaborative studies using shared NMOSD data are needed to suitably define factors related to COVID-19 severity and neurologic manifestations.

Sarcoidosis and neuromyelitis optica in a patient with optic neuritis - a case report.

We present a case of atypical recurrent optic neuritis. A man in his 50s presented with right optic neuritis and profound visual loss, associated with elevated inflammatory markers. Lymph-node biopsy was consistent with sarcoidosis. Aquaporin-4 antibodies were also present. Three months following corticosteroid treatment, his right optic neuritis relapsed, again with raised inflammatory markers. He was started on azathioprine and prednisolone with good effect. A dual diagnosis of sarcoidosis and neuromyelitis optica with aquaporin-4 antibodies is very rare. Long-term immunosuppression is required. The case highlights the importance of identifying the features and cause of atypical optic neuritis.

Pain, Depression, and Quality of Life in Neuromyelitis Optica Spectrum Disorder: A Cross-Sectional Study of 166 AQP4 Antibody-Seropositive Patients.

OBJECTIVES: To evaluate prevalence, clinical characteristics, and predictors of pain, depression, and their impact on the quality of life (QoL) in a large neuromyelitis optica spectrum disorder (NMOSD) cohort. METHODS: We included 166 patients with aquaporin-4-seropositive NMOSD from 13 tertiary referral centers. Patients received questionnaires on demographic and clinical characteristics, PainDetect, short form of Brief Pain Inventory, Beck Depression Inventory-II, and Short Form 36 Health Survey. RESULTS: One hundred twenty-five (75.3%) patients suffered from chronic NMOSD-associated pain. Of these, 65.9% had neuropathic pain, 68.8% reported spasticity-associated pain and 26.4% painful tonic spasms. Number of previous myelitis attacks (OR = 1.27, p = 0.018) and involved upper thoracic segments (OR = 1.31, p = 0.018) were the only predictive factors for chronic pain. The latter was specifically associated with spasticity-associated pain (OR = 1.36, p = 0.002). More than a third (39.8%) suffered from depression, which was moderate to severe in 51.5%. Pain severity (OR = 1.81, p < 0.001) and especially neuropathic character (OR = 3.44, p < 0.001) were associated with depression. Pain severity and walking impairment explained 53.9% of the physical QoL variability, while depression and walking impairment 39.7% of the mental QoL variability. No specific medication was given to 70.6% of patients with moderate or severe depression and 42.5% of those with neuropathic pain. Two-thirds (64.2%) of patients with symptomatic treatment still reported moderate to severe pain. CONCLUSIONS: Myelitis episodes involving upper thoracic segments are main drivers of pain in NMOSD. Although pain intensity was lower than in previous studies, pain and depression remain undertreated and strongly affect QoL. Interventional studies on targeted treatment strategies for pain are urgently needed in NMOSD.

Autoantibodies Against the Complement Regulator Factor H in the Serum of Patients With Neuromyelitis Optica Spectrum Disorder.

Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune inflammatory disease of the central nervous system (CNS), characterized by pathogenic, complement-activating autoantibodies against the main water channel in the CNS, aquaporin 4 (AQP4). NMOSD is frequently associated with additional autoantibodies and antibody-mediated diseases. Because the alternative pathway amplifies complement activation, our aim was to evaluate the presence of autoantibodies against the alternative pathway C3 convertase, its components C3b and factor B, and the complement regulator factor H (FH) in NMOSD. Four out of 45 AQP4-seropositive NMOSD patients (~9%) had FH autoantibodies in serum and none had antibodies to C3b, factor B and C3bBb. The FH autoantibody titers were low in three and high in one of the patients, and the avidity indexes were low. FH-IgG complexes were detected in the purified IgG fractions by Western blot. The autoantibodies bound to FH domains 19-20, and also recognized the homologous FH-related protein 1 (FHR-1), similar to FH autoantibodies associated with atypical hemolytic uremic syndrome (aHUS). However, in contrast to the majority of autoantibody-positive aHUS patients, these four NMOSD patients did not lack FHR-1. Analysis of autoantibody binding to FH19-20 mutants and linear synthetic peptides of the C-terminal FH and FHR-1 domains, as well as reduced FH, revealed differences in the exact binding sites of the autoantibodies. Importantly, all four autoantibodies inhibited C3b binding to FH. In conclusion, our results demonstrate that FH autoantibodies are not uncommon in NMOSD and suggest that generation of antibodies against complement regulating factors among other autoantibodies may contribute to the complement-mediated damage in NMOSD.

Autoantibodies in neurological disease.

The realization that autoantibodies can contribute to dysfunction of the brain has brought about a paradigm shift in neurological diseases over the past decade, offering up important novel diagnostic and therapeutic opportunities. Detection of specific autoantibodies to neuronal or glial targets has resulted in a better understanding of central nervous system autoimmunity and in the reclassification of some diseases previously thought to result from infectious, 'idiopathic' or psychogenic causes. The most prominent examples, such as aquaporin 4 autoantibodies in neuromyelitis optica or NMDAR autoantibodies in encephalitis, have stimulated an entire field of clinical and experimental studies on disease mechanisms and immunological abnormalities. Also, these findings inspired the search for additional autoantibodies, which has been very successful to date and has not yet reached its peak. This Review summarizes this rapid development at a point in time where preclinical studies have started delivering fundamental new data for mechanistic understanding, where new technologies are being introduced into this field, and - most importantly - where the first specifically tailored immunotherapeutic approaches are emerging.

Investigating the Presence of Interattack Astrocyte Damage in Neuromyelitis Optica Spectrum Disorder: Longitudinal Analysis of Serum Glial Fibrillary Acidic Protein.

OBJECTIVES: Information on subclinical astrocyte damage can provide further insight into neuromyelitis optica spectrum disorder (NMOSD) pathophysiology and disease-monitoring strategies. To investigate whether astrocyte and neuroaxonal damage occurs during interattack periods in individuals with NMOSD through longitudinal measurement of serum glial fibrillary acidic protein (sGFAP) and neurofilament light chain (sNfL) at multiple time points. METHODS: sGFAP and sNfL levels were measured in 187 serum samples from 20 participants with NMOSD treated with rituximab (median follow-up: 24 months) and 19 age-/sex-matched healthy controls using a highly sensitive single-molecule array assay. From the NMOSD cohort of National Cancer Center, Korea, 14 clinically stable participants were randomly selected for focused investigation of interattack periods, and 6 participants with clinical attacks despite treatment were enrolled for attack-related measurements. RESULTS: Significant elevations of sGFAP levels were observed in all clinical attacks, and 95% (19/20) of patients showed reduction of sGFAP levels below the cutoff value (3 SDs above mean levels in age-/sex-matched healthy controls) within 3 months of their clinical attacks. The sGFAP levels were consistently low during interattack periods in 90% (17/19) of patients whose sGFAP levels returned to below the cutoff value. Changes in sNfL levels were similar to but slower than those in sGFAP levels. CONCLUSIONS: Subclinical astrocyte damage represented by increasing sGFAP levels rarely occurred during interattack periods in individuals with NMOSD; however, a certain degree of astrocyte damage did occur at the time of clinical attacks without exception, but it was not evident within 3 months of the attack.

The possible role of Interleukin-6 as a regulator of insulin sensitivity in patients with neuromyelitis optica spectrum disorder.

BACKGROUND: Neuromyelitis optica spectrum disorder (NMOSD) is associated with inflammatory mediators that may also trigger downstream signaling pathways leading to reduce insulin sensitivity. METHODS: We aimed to determine the risk association of hyperinsulinemia in NMOSD patients with seropositive AQP4-IgG and the serum levels of interleukin (IL)-6 and IL-17A compared with the control group. Serum levels of metabolic (Insulin, Fasting Blood Sugar (FBS), lipid profile) and inflammatory (IL-6 and IL-17) markers were assessed in 56 NMOSD patients and 100 controls. RESULTS: Hyperinsulinemia was more prevalent in NMOSD patients independent of age, sex and body mass index (BMI) (48.2% vs. 26%, p = 0.005) compared to control group. After adjusting age, sex and BMI, there was significant association between lower insulin sensitivity (IS) and NMOSD risk (95% CI: Beta = 0.73, 0.62 to 0.86, p = 0.0001). Circulating levels of IL-6 and IL-17 were higher in NMOSD patients, and only IL-6 had an effect modifier for the association between lower insulin sensitivity and NMOSD risk. CONCLUSIONS: Our data suggests that inflammatory pathogenesis of NMOSD leads to hyperinsulinemia and increases the risk of insulin resistance.

Neuromyelitis optica spectrum disorder (NMOSD) presenting as acute transverse myelitis with positive aquaporin 4 antibodies.

An 80-year-old, previously healthy patient presents with acute transverse myelitis with sensory level at T8. The MRI scan of the spinal cord showed longitudinal extensive transverse myelitis, and she tested positive for aquaporin 4 antibodies in serum. She received treatment with intravenous and oral steroids, with no improvement and then underwent plasma exchange. She was then started on azathioprine for prevention of relapses, while continuing physiotherapy and occupational therapy. Eventually, she was transferred to a specialised spinal cord centre for long-term rehabilitation.

Prognostic factors for relapse and outcome in pediatric acute transverse myelitis.

OBJECTIVE: It may be difficult for clinicians to estimate the prognosis of pediatric acute transverse myelitis (ATM). The aim of this study was to define prognostic factors for relapsing disease and poor outcome in pediatric ATM. METHODS: This prospective cohort study included 49 children, 18 boys and 31 girls (median age 13.1 years, IQR 6.5-16.2) with a first episode of ATM. Factors associated with relapsing disease and poor outcome (Expanded Disability Status Scale (EDSS) ≥ 4) were assessed during a median follow-up of 37 months (IQR 18-75). RESULTS: In total, 14 patients (29%) experienced ≥ 1 relapse(s) and nine patients (18%) had a poor outcome. Factors at onset associated with relapsing disease included higher age (16.1 vs. 11.6 years, p = 0.002), longer time to maximum severity of symptoms (5.5 vs. 3 days, p = 0.01), lower maximum EDSS score (4.0 vs. 6.5, p = 0.003), short lesion on spinal MRI (64 vs. 21%, p = 0.006), abnormalities on brain MRI (93 vs. 44%, p = 0.002) and presence of oligoclonal bands in cerebrospinal fluid (67 vs. 14%, p = 0.004). The only factor associated with poor outcome was presence of a spinal cord lesion on MRI without cervical involvement (56 vs. 14%, p = 0.02). CONCLUSION: Pediatric ATM patients presenting with clinical, radiological and laboratory features associated with multiple sclerosis (MS) are at risk for relapsing disease. In absence of these known MS risk factors at onset of disease these patients are at low risk for relapses. Only a minority of pediatric ATM patients in this cohort have a poor outcome.

Epidemiology of Demyelinating Diseases in Korean Pediatric Patients.

The epidemiology of demyelinating diseases in the Korean pediatric population has not been reported to date. This study aimed to identify the epidemiology of demyelinating diseases in Korean children by using big data. The subjects were children (0-17 years old) diagnosed with acute-disseminated encephalomyelitis, multiple sclerosis, neuromyelitis optica, and Guillain-Barré syndrome enrolled in the Korean Health Insurance Review and Assessment Service (HIRA) from January 2010 to December 2017.Of 1722 enrolled children, 553 (32.1%) had acute-disseminated encephalomyelitis, 170 (9.9%) had multiple sclerosis, 68 (3.9%) had neuromyelitis optica, and 931 (54.1%) had Guillain-Barré syndrome. The male-female ratios were 1.47:1 in acute-disseminated encephalomyelitis, 1.43:1 in Guillain-Barré syndrome, 1:1.66 in multiple sclerosis, and 1:1.62 in neuromyelitis optica. Demyelinating diseases were most prevalent in summer. The prevalence differed by region, with 545 (31.6%) in Seoul and 298 (17.3%) in Gyeonggi. This study is the first to identify the incidence of demyelinating diseases in South Korea.

Comparison of macular structural and vascular changes in neuromyelitis optica spectrum disorder and primary open angle glaucoma: a cross-sectional study.

AIMS: To compare macular structure and vasculature between neuromyelitis optica spectrum disorder (NMOSD) and primary open angle glaucoma (POAG) using optical coherence tomography angiography. METHODS: NMOSD patients (n=124) with/without a history of optic neuritis (ON) (NMO+ON: 113 eyes; NMO-ON: 95 eyes), glaucomatous patients (n=102) with early/advanced glaucoma (G-E: 74 eyes; G-A: 50 eyes) and healthy controls (n=62; 90 eyes) were imaged. The main outcome measures were macular ganglion cell-inner plexiform layer (GC-IPL) thickness, vessel density (VD) and perfusion density (PD) in the superficial capillary plexus, and diagnostic capabilities of the parameters as calculated by area under the curve (AUC). RESULTS: Significant losses in GC-IPL, VD and PD were detected in both patients with NMOSD and POAG. With matched losses in the peripapillary retinal nerve fibre layer, NMOSD group showed significant thinning of GC-IPL in the nasal-superior quadrant, whereas in POAG group, significant thinning was observed in the inferior and temporal-inferior quadrants. GC-IPL thinning was more prominent in the superior, nasal-superior and nasal-inferior quadrants in NMO+ON eyes. In G-A eyes, significant GC-IPL thinning was seen in the temporal-inferior quadrant. The specific structural parameters combining VD and foveal avascular zone (FAZ) indices showed the best diagnostic accuracies. The FAZ area in eyes with NMOSD was significantly smaller than the eyes of healthy controls and POAG. CONCLUSION: NMOSD and POAG have specific patterns of macular structural and vascular changes associated with pathophysiology. Our results indicate that FAZ could be a sensitive biomarker of macular changes in NMOSD.

Neuromielitis óptica: reporte de un caso clínico / Optic neuromyelitis: a clinical case report

La neuromielitis óptica (NMO) y los trastornos del espectro de neuromielitis óptica (NMOSD) son trastornos poco frecuentes, mediados por anticuerpos del sistema nervioso central (SNC) con predilección por la médula espinal y los nervios ópticos. Existe una fuerte predilección femenina. En el caso de la forma recurrente más común de la enfermedad, que representa del 80% al 90% de los casos, las mujeres están sobrerrepresentadas con una proporción de 5 a 10: 1.6. La edad media de inicio es de 39,7 años. Objetivo: Determinar la causa de neuromielitis óptica en paciente femenina de 24 años de edad. Materiales y métodos: Es una investigación enmarcada en el paradigma positivista, con enfoque cuantitativo. Con un estudio de campo-descriptivo, no experimental, en la modalidad de caso clínico único. El método utilizado fue la historia clínica y consentimiento informado. Resultado: Se presenta el caso de una paciente de sexo femenino de 24 años de edad, sin antecedentes patológicos personales. Presentó pérdida progresiva de la visión de 2 meses de evolución, que se acompañaba de dolor en región cervical de moderada intensidad y en 24 horas presentó parestesia en brazo derecho, afasia, cuadro neurológico que evolucionó hasta presentar cuadriparesia, insuficiencia respiratoria aguda. Conclusión: En IRM de columna cervical se evidencia cambio anormal de la señal medular cervical evidente en secuencias T2 flair lesión hiperintensa longitudinalmente extensa que abarca más de 3 cuerpos vertebrales. Fue tratada con corticoides y plasmaféresis(AU)

Neuromielitis optic (NMO) and neuromielitis optic spectrum disorders (NMOSD) are rare disorders mediated by antibodies of the central nervous system (CNS) with a predilection for the spinal cord and optic nerves. There is a strong female predilection. In the case of the most common recurrent form of the disease, which accounts for 80% to 90% most of the cases are women with a ratio of five to 10: 1.6. The mean age of onset is 39.7 years. Objective: To determine the cause of neuromielitis optica in a 24-year-old female patient. Materials and methods: It is an investigation framed in the positivist paradigm, with a quantitative approach. With a descriptive field study, not experimental, in the single clinical case modality. The method used was the medical history and informed consent. Result: The case of a 24-year-old female patient with no presented personal pathological history. She presented progressive loss of vision of 2 months of evolution, accompanied by pain in the cervical region of moderate intensity and within 24 hours, she presented paresthesia in the right arm, aphasia, a neurological picture that evolved until presenting cuadriparesia, acute respiratory failure. Conclusion: An MRI of the cervical spine shows an abnormal change in the cervical spinal signal evident in T2 sequences flair a longitudinally extensive hiperintensa lesion that encompasses more than 3 vertebral bodies. Her treatment was corticosteroids and plasmapheresis(AU)

Neuromyelitis optica.

Neuromyelitis optica (NMO; also known as Devic syndrome) is a clinical syndrome characterized by attacks of acute optic neuritis and transverse myelitis. In most patients, NMO is caused by pathogenetic serum IgG autoantibodies to aquaporin 4 (AQP4), the most abundant water-channel protein in the central nervous system. In a subset of patients negative for AQP4-IgG, pathogenetic serum IgG antibodies to myelin oligodendrocyte glycoprotein, an antigen in the outer myelin sheath of central nervous system neurons, are present. Other causes of NMO (such as paraneoplastic disorders and neurosarcoidosis) are rare. NMO was previously associated with a poor prognosis; however, treatment with steroids and plasma exchange for acute attacks and with immunosuppressants (in particular, B cell-depleting agents) for attack prevention has greatly improved the long-term outcomes. Recently, a number of randomized controlled trials have been completed and the first drugs, all therapeutic monoclonal antibodies, have been approved for the treatment of AQP4-IgG-positive NMO and its formes frustes.