Epidemiology of neuromyelitis optica spectrum disorder and its prevalence and incidence worldwide

Neuromyelitis optica spectrum disorder (NMOSD) is an uncommon inflammatory disease of the central nervous system, manifesting clinically as optic neuritis, myelitis, and certain brain and brainstem syndromes. Cases clinically diagnosed as NMOSD may include aquaporin 4 (AQP4)-antibody-seropositive autoimmune astrocytopathic disease, myelin oligodendrocyte glycoprotein (MOG)-antibody-seropositive inflammatory demyelinating disease, and double-seronegative disease. AQP4-antibody disease has a high female-to-male ratio (up to 9:1), and its mean age at onset of ~40 years is later than that seen in multiple sclerosis. For MOG-antibody disease, its gender ratio is closer to 1:1, and it is more common in children than in adults. Its clinical phenotypes differ but overlap with those of AQP4-antibody disease and include acute disseminated encephalomyelitis, brainstem and cerebral cortical encephalitis, as well as optic neuritis and myelitis. Double-seronegative disease requires further research and clarification. Population-based studies over the past two decades report the prevalence and incidence of NMOSD in different populations worldwide. One relevant finding is the varying prevalence observed in different racial groups. Consistently, the prevalence of NMOSD among Whites is ~1/100,000 population, with an annual incidence of <1/million population. Among East Asians, the prevalence is higher, at ~3.5/100,000 population, while the prevalence in Blacks may be up to 10/100,000 population. For MOG-antibody disease, hospital-based studies largely do not observe any significant racial preponderance so far. This disorder comprises a significant proportion of NMOSD cases that are AQP4-antibody-seronegative. A recent Dutch nationwide study reported the annual incidence of MOG-antibody disease as 1.6/million population (adult: 1.3/million, children: 3.1/million). Clinical and radiological differences between AQP4-antibody and MOG-antibody associated diseases have led to interest in the revisions of NMOSD definition and expanded stratification based on detection of a specific autoantibody biomarker. More population-based studies in different geographical regions and racial groups will be useful to further inform the prevalence and incidence of NMOSD and their antibody-specific subgroups. Accessibility to AQP4-antibody and MOG-antibody testing, which is limited in many centers, is a challenge to overcome. Environmental and genetic studies will be useful accompaniments to identify other potential pathogenetic factors and specific biomarkers in NMOSD

Z historii zapalenia rdzenia i nerwów wzrokowych

Terminu „zapalenie rdzenia i nerwów wzrokowych” ([NMO, neuro-myelitis optica], choroba Devica) użyli po raz pierwszy w roku 1894 Eugène Devic i Fernand Gault. Jest to rzadka choroba (ok. 1% zachorowań na choroby demielinizacyjne ośrodkowego ukła-du nerwowego), w której proces autoimmunologiczny powodu-je zapalenie rdzenia kręgowego i nerwów wzrokowych, a w kon­sekwencji — ich demielinizację. Zespół Devica jest często mylony z początkowym okresem stwardnienia rozsianego, jednak wymaga odmiennego leczenia. Głównymi objawami NMO są niedowłady kończyn, zaburzenia czucia, dysfunkcja neurogenna pęcherza moczowego i zaburzenia widzenia aż do utraty wzroku. Mediana wieku zachorowania na NMO przypada na 39. rok życia, 85% chorych to kobiety. Rokowa­nie może być niepomyślne, dlatego istotne znaczenie mają decyzje terapeutyczne podjęte na wczesnym etapie choroby. Współwystępowanie objawów zapalenia nerwów wzrokowych i zapalenia rdzenia kręgowego opisywano długo przed doniesie­niami Devica i Gaulta. Kamieniem milowym w historii NMO stało się odkrycie przeciwciał przeciw akwaporynie 4. Kolejny etap to rozwój badań nad przeciwciałami antyMOG. Nadal istnieją jednak postacie NMO, w których nie stwierdza się obecności żadnego z powyższych przeciwciał. W niniejszym artykule przeglądowym przedstawiono w skrócie historię neuromyelitis optica, ze szcze­gólnym uwzględnieniem wkładu badaczy polskich

Collaborative International Research in Clinical and Longitudinal Experience Study in NMOSD

OBJECTIVE: To develop a resource of systematically collected, longitudinal clinical data and biospecimens for assisting in the investigation into neuromyelitis optica spectrum disorder (NMOSD) epidemiology, pathogenesis, and treatment. METHODS: To illustrate its research-enabling purpose, epidemiologic patterns and disease phenotypes were assessed among enrolled subjects, including age at disease onset, annualized relapse rate (ARR), and time between the first and second attacks. RESULTS: As of December 2017, the Collaborative International Research in Clinical and Longitudinal Experience Study (CIRCLES) had enrolled more than 1,000 participants, of whom 77.5% of the NMOSD cases and 71.7% of the controls continue in active follow-up. Consanguineous relatives of patients with NMOSD represented 43.6% of the control cohort. Of the 599 active cases with complete data, 84% were female, and 76% were anti-AQP4 seropositive. The majority were white/Caucasian (52.6%), whereas blacks/African Americans accounted for 23.5%, Hispanics/Latinos 12.4%, and Asians accounted for 9.0%. The median age at disease onset was 38.4 years, with a median ARR of 0.5. Seropositive cases were older at disease onset, more likely to be black/African American or Hispanic/Latino, and more likely to be female. CONCLUSION: Collectively, the CIRCLES experience to date demonstrates this study to be a useful and readily accessible resource to facilitate accelerating solutions for patients with NMOSD

Collaborative International Research in Clinical and Longitudinal Experience Study in NMOSD

Objective To develop a resource of systematically collected, longitudinal clinical data and biospecimens for assisting in the investigation into neuromyelitis optica spectrum disorder (NMOSD) epidemiology, pathogenesis, and treatment. Methods To illustrate its research-enabling purpose, epidemiologic patterns and disease phenotypes were assessed among enrolled subjects, including age at disease onset, annualized relapse rate (ARR), and time between the first and second attacks. Results As of December 2017, the Collaborative International Research in Clinical and Longitudinal Experience Study (CIRCLES) had enrolled more than 1,000 participants, of whom 77.5% of the NMOSD cases and 71.7% of the controls continue in active follow-up. Consanguineous relatives of patients with NMOSD represented 43.6% of the control cohort. Of the 599 active cases with complete data, 84% were female, and 76% were anti-AQP4 seropositive. The majority were white/Caucasian (52.6%), whereas blacks/African Americans accounted for 23.5%, Hispanics/ Latinos 12.4%, and Asians accounted for 9.0%. The median age at disease onset was 38.4 years, with a median ARR of 0.5. Seropositive cases were older at disease onset, more likely to be black/African American or Hispanic/Latino, and more likely to be female. Conclusions Collectively, the CIRCLES experience to date demonstrates this study to be a useful and readily accessible resource to facilitate accelerating solutions for patients with NMOSD

Longitudinal retinal changes in MOGAD

OBJECTIVE: Patients with myelin oligodendrocyte glycoprotein antibody (MOG-IgG) associated disease (MOGAD) suffer from severe optic neuritis (ON) leading to retinal neuro-axonal loss, which can be quantified by optical coherence tomography (OCT). We assessed whether ON-independent retinal atrophy can be detected in MOGAD. METHODS: Eighty MOGAD patients and 139 healthy controls (HC) were included. OCT data was acquired with 1) Spectralis spectral domain OCT (MOGAD (N=66) and HC (N=103)) and 2) Cirrus HD-OCT (MOGAD (N=14) and HC (N=36)). Macular combined ganglion cell and inner plexiform layer (GCIPL) and peripapillary retinal nerve fibre layer (pRNFL) were quantified. RESULTS: At baseline, GCIPL and pRNFL were lower in MOGAD eyes with a history of ON (MOGAD-ON) compared with MOGAD eyes without a history of ON (MOGAD-NON) and HC (p12 months ago (p<0.001). The overall MOGAD cohort did not exhibit faster GCIPL thinning compared with HC. INTERPRETATION: Our study suggests the absence of attack-independent retinal damage in MOGAD. Yet, ongoing neuroaxonal damage or oedema resolution seems to occur for up to 12 months after ON, which is longer than what has been reported with other ON forms. These findings support that the pathomechanisms underlying optic nerve involvement and the evolution of OCT retinal changes after ON is distinct in MOGAD. This article is protected by copyright. All rights reserved

Collaborative International Research in Clinical and Longitudinal Experience Study in NMOSD.

Objective: To develop a resource of systematically collected, longitudinal clinical data and biospecimens for assisting in the investigation into neuromyelitis optica spectrum disorder (NMOSD) epidemiology, pathogenesis, and treatment. Methods: To illustrate its research-enabling purpose, epidemiologic patterns and disease phenotypes were assessed among enrolled subjects, including age at disease onset, annualized relapse rate (ARR), and time between the first and second attacks. Results: As of December 2017, the Collaborative International Research in Clinical and Longitudinal Experience Study (CIRCLES) had enrolled more than 1,000 participants, of whom 77.5% of the NMOSD cases and 71.7% of the controls continue in active follow-up. Consanguineous relatives of patients with NMOSD represented 43.6% of the control cohort. Of the 599 active cases with complete data, 84% were female, and 76% were anti-AQP4 seropositive. The majority were white/Caucasian (52.6%), whereas blacks/African Americans accounted for 23.5%, Hispanics/Latinos 12.4%, and Asians accounted for 9.0%. The median age at disease onset was 38.4 years, with a median ARR of 0.5. Seropositive cases were older at disease onset, more likely to be black/African American or Hispanic/Latino, and more likely to be female. Conclusions: Collectively, the CIRCLES experience to date demonstrates this study to be a useful and readily accessible resource to facilitate accelerating solutions for patients with NMOSD

Retinal degeneration in MOG antibody Associated Disease (MOGAD): a longitudinal OCT study

Background and aims.Since in MOGAD(MOG antibody Associated Disease)data about prognostic meaning of MOG ab titres and retinal degeneration are still lacking, we analysed longitudinal dynamics of MOG antibodies and of GCL and RNFL thicknesses, acquired through OCT scans in a cohort of MOGAD patients. We compared GCL and RNFL thicknesses and dynamics between MOGAD patients and a cohort of multiple sclerosis(MS) patients. Methods.Prospective and retrospective interventistic monocentric study. MOGAD and MS patients referring to Mondino Foundation underwent periodic clinical and serological follow-up(FU)and OCT scans. Results.MOGAD cohort was made up of 16 patients, with mean age of 38 years, mean EDSS of 1.8, mean FU duration of 49 months. 8/16 patients showed a relapsing form of disease.MOG ab titres dynamics were similar between monophasic and relapsing patients. However, in 5/8 relapsing patients clinical relapse occurred in concomitance with increasing in MOGab titres. We didn’t find correlation between MOG antibody titres at baseline and mean GCL-RNFL thicknesses,and between MOG ab titres and OCT thicknesses variation rates. Patients were divided in groups according to history of optic neuritis(ON): MOG-ON+(N=11) and MOG-ON-(N=5). Mean MOG antibody titres at baseline were similar between groups, as baseline OCT thicknesses. We didn’t find differences in GCL-RNFL variation rates between groups.We didn’t find correlations between MOG dynamics and GCL-RNFL thinning rates considering eyes with and without ON. Considering whole cohort of MOGAD, we found association between annualized GCL variation rate and relapsing course of disease(p=0.01). This result also applied when splitting our cohort into MOG-ON+and MOG-ON-subgroups. Considering EDSS variation at FU, annualized CGL variation rate was higher in patients with disability progression(p=0.03). MS cohort was made up of 21 patients, with mean age of 34 years,mean EDSS of 1,mean FU duration of 40 months. Demographic features were similar between MOGAD and MS,except for baseline EDSS, which was higher in MOGAD and sex(F/M ratio was higher in RRMS cohort). Considering patients with ON, GCL-RNFL baseline thicknesses and thinning rates were similar between MOGAD and MS.Considering eyes without history of ON, we found a higher annualized GCL variation rate in MOGAD(p=0.03). This result applied when considering group of unaffected eyes(p=0.05), but didn’t apply when considering group of fellow eyes. Discussion and conclusions. Even if MOG ab titres dynamics didn’t differ between monophasic and relapsing patients, the occurrence of clinical relapses is preceded by an increasing in MOG ab titres. Thus, monitoring MOG-ab titres could have a prognostic utility. In MOGAD cohort, retinal degeneration was higher in relapsing patients, independently of the occurrence of ON. Thus, retinal degeneration could be accelerated by inflammatory events, independently of the district in which they occur. MOG ab titres didn’t correlate with retinal degeneration. Thus, monitoring MOG ab titres might not reflect severity of retinal degeneration, even in eyes with history of ON. All patients experiencing disability progression show increased MOG ab titres at FU and faster GCL thinning rates. As titres increased during relapses and retinal degeneration accelerates after inflammatory episodes, these data highlight the concept that retinal degeneration and disability progression could be result of recurrent relapses. Retinal degeneration is similar in MOGAD and MS eyes with ON as in fellow eyes. Thus, we could infer that retinal degeneration is independent of the triggering ON. Moreover, in fellow eyes, a similar physiopathological mechanism could occur. In eyes without ON retinal degeneration is higher in MOGAD than in MS.This data question if, even in MOGAD, a pure neurodegenerative process could exist thus considering that disability progression could not be caused only by clinical relapses

Cohort profile: a collaborative multicentre study of retinal optical coherence tomography in 539 patients with neuromyelitis optica spectrum disorders (CROCTINO)

PURPOSE: Optical coherence tomography (OCT) captures retinal damage in neuromyelitis optica spectrum disorders (NMOSD). Previous studies investigating OCT in NMOSD have been limited by the rareness and heterogeneity of the disease. The goal of this study was to establish an image repository platform, which will facilitate neuroimaging studies in NMOSD. Here we summarise the profile of the Collaborative OCT in NMOSD repository as the initial effort in establishing this platform. This repository should prove invaluable for studies using OCT to investigate NMOSD. PARTICIPANTS: The current cohort includes data from 539 patients with NMOSD and 114 healthy controls. These were collected at 22 participating centres from North and South America, Asia and Europe. The dataset consists of demographic details, diagnosis, antibody status, clinical disability, visual function, history of optic neuritis and other NMOSD defining attacks, and OCT source data from three different OCT devices. FINDINGS TO DATE: The cohort informs similar demographic and clinical characteristics as those of previously published NMOSD cohorts. The image repository platform and centre network continue to be available for future prospective neuroimaging studies in NMOSD. For the conduct of the study, we have refined OCT image quality criteria and developed a cross-device intraretinal segmentation pipeline. FUTURE PLANS: We are pursuing several scientific projects based on the repository, such as analysing retinal layer thickness measurements, in this cohort in an attempt to identify differences between distinct disease phenotypes, demographics and ethnicities. The dataset will be available for further projects to interested, qualified parties, such as those using specialised image analysis or artificial intelligence applications

Clinical and epidemiological study of Devicʼs disease in Central Serbia

Neuromijelitis optika spektar bolesti (NMOSB), odnosno Devikova bolest, je akvaporin-4 autoantitelom-posredovano demijelinizaciono oboljenje centralnog nervnog sistema, koje dovodi do teškog stepena neurološke onesposobljenosti, vezane najčešće za vizuelni i motorni sistem, ali i do značajnog letaliteta. Ciljevi: Analiza demografskih, kliničkih i parakliničkih karakteristika bolesnika sa NMOSB u Centralnoj Srbiji i procena njihovog uticaja na dugotrajni ishod bolesti. Osim toga, procenjivana je prevalencija NMOSB u Centralnoj Srbiji. Bolesnici i metode: U istraživanje uticaja različitih demografskih, kliničkih i parakliničkih karakteristika na dugotrajni ishod bolesti je uključeno 74 bolesnika koji ispunjavaju nove kriterijume iz 2015. godine za NMOSB iz hospitalnog registra obolelih Klinike za neurologiju Kliničkog centra Srbije (KCS). Svi relevantni podaci prikupljani su iz bolničke dokumentacije. Neurološka onesposobljenost je kvantifikovana primenom proširene skale stepena neurološke onesposobljenosti (engl. Expanded disability status scale, EDSS) i Optikospinalnom skalom onesposobljenosti (engl. Opticospinal impairement scale, OSIS), sa vizuelnim i motornim subskorovima. Prevalencija NMOSB je izračunata primenom standardnih procedura na osnovu podataka iz Populacionog NMOSB registra Centralne Srbije. Rezultati: Relapsno remitentni tok bolesti je imalo 82,4% obolelih. Seropozitivnost AQP4-IgG je ustanovljena kod 89.2% obolelih. Četrdeset pet od 74 bolesnika su lečeni imunosupresivnom terapijom (40 – azatioprin, 3 – mikofenolat mofetil, 1 - ciklofosfamid, 1 - mitoksantron, i 2 - rituksimab). Srednje vreme od početka bolesti do dostizanja EDSS skora 4.0 bilo je 6.5 godina, do EDSS 6.0 bilo je 11.9 godina, i do EDSS 7.0 bilo je 22.0 godine. Faktor za koji je pokazano da povećava rizik za dostizanje EDSS 4.0, 6.0 i 7.0 je inicijalno veći EDSS. Takođe, kraći prvi inter-relapsni interval je povećavao rizik za dostizanje EDSS 4.0 i 6.0, a duže vreme od početka bolesti do uvođenja terapije održavanja, rizik za dostizanje EDSS 7.0. Veći stepen onesposobljenosti koji se odnosi na vidnu funkciju na početku bolesti bio je prediktor bržeg dostizanja OSIS VA = 6 i VA = 8 (engl. Visual acuity, VA). Teška vidna onesposobljenost (OSIS VA 6) je ranije dostignuta, ukoliko je bolest počela sa optičkim neuritisom (medijana,10,0 godina) ili optikospinalnim sindromom (medijana, 11,4 godina), nego posle početka 6 bolesti mijelitisom (medijana, 18,0 godina) (p=0,002). Procenjena prevalencija NMOSB u Centralnoj Srbiji je 1,03/100 000...Introduction: Neuromyelitis optica spectrum disorders (NMOSD), or Devic's disease, is an antiaquaporin- 4 autoantibody mediated, demyelinating disease of the central nervous system, which leads to severe visual and motor disability, and significant case fatality. Aim: Analysis of demographic, clinical and paraclinical characteristics of patients with NMOSD in the Central Serbia and assessment of their impact on the long-term outcome of the disease. Assessment of this disease prevalence, in the same region. Patients and methods: This study included 74 patients who met the latest 2015 NMOSD diagnostic criteria, from the hospital registry based at the Neurology clinic, Clinical Center of Serbia (CCS). All relevant demographic, clinical and paraclinical data were collected from hospital records. Neurological disability was assessed using the Extended Disability Status Scale (EDSS) score and the Opticospinal Impairment Scale (OSIS), with visual and motor sub scores. The NMOSD prevalence was calculated by standard procedures based on the data from the Central Serbia Registry for NMOSD. Results: 82.4% of patients had a relapsing-remitting course of the disease. Seropositivity of AQP4-IgG was found in 89.2% of patients. 45 out of 74 patients were treated with immunosuppressive therapy (40 - azathioprine, 3 - mycophenolate mofetil, 1 - cyclophosphamide, 1 - mitoxantrone, and 2 rituximab). The median time from disease onset to EDSS score 4.0 was 6.5 years, EDSS 6.0 11.9 years, and EDSS 7.0 22.0 years. Higher baseline EDSS was associated with higher risk of attaining EDSS 4.0, 6.0 and 7.0; a shorter first inter-attack interval increased the risk for reaching EDSS 4.0 and 6.0; longer time from the disease onset to the start of treatment administration increased the risk for reaching EDSS 7.0. Worse visual acuity at the disease onset predicted faster assignment of OSIS VA = 6 and VA = 8. Severe visual deficit (OSIS VA 6) was reached earlier after optic neuritis (median time,10.0 years) or combined opticospinal onset (median time, 11.4 years) than after myelitis onset (median time, 18.0 years) (p=0.002). Estimated prevalence of NMOSD in Central Serbia is 1.03/100 000..