Seasonal distribution of attacks in aquaporin-4 antibody disease and myelin-oligodendrocyte antibody disease

doi:10.1016/j.jns.2020.116881

Journal of the Neurological Sciences

Volume 415, 15 August 2020, 116881

https://doi.org/10.1016/j.jns.2020.116881 Get rights and content

Highlights

•
Seasonal variation has been reported for some neuroinflammatory conditions, like MS.
•
It is unknown whether seasonality also influences AQP4- and MOG-antibody disease.
•
In contrast to MS, we found no seasonal variation of attacks in these diseases.

Abstract

Background

Seasonal variation in incidence and exacerbations has been reported for neuroinflammatory conditions such as multiple sclerosis and acute disseminated encephalomyelitis (ADEM). It is unknown whether seasonality also influences aquaporin-4 antibody (AQP4-Ab) disease and myelin-oligodendrocyte antibody (MOG-Ab) disease.

Objective

We examined the seasonal distribution of attacks in AQP4-Ab disease and MOG-Ab disease.

Methods

Observational study using data prospectively recorded from three cohorts in the United Kingdom.

Results

There was no clear seasonal variation in AQP4-Ab or MOG-Ab attacks for either the onset attack nor subsequent relapses. In both groups, the proportion of attacks manifesting with each of the main phenotypes (optic neuritis, transverse myelitis, ADEM/ADEM-like) appeared stable across the year. This study is the first to examine seasonal distribution of MOG-Ab attacks and the largest in AQP4-Ab disease so far.

Conclusion

Lack of seasonal distribution in AQP4-Ab and MOG-Ab disease may argue against environment factors playing a role in the aetiopathogenesis of these conditions.

Introduction

Antibodies against aquaporin-4 (AQP4-Ab) and myelin-oligodendrocyte glycoprotein (MOG-Ab) are now recognised to cause neuromyelitis optica spectrum disorders (NMOSD), acute disseminated encephalomyelitis (ADEM) and, more rarely, with MOG-Ab, cortical encephalitis [[1], [2], [3]]. These antibodies are believed to be pathogenic, causing a primary astrocytopathy (AQP4-Ab) and a primary demyelinating disorder (MOG-Ab) [4,5]. Despite major advances in the understanding of their pathophysiology, putative triggers of autoimmunity in these conditions are yet to be identified.

Seasonal variation in manifestations of disease may reflect changes in environmental factors, some of which hold the potential to trigger or modulate biological processes involved in autoimmunity [6]. If present, a seasonal pattern may aid in the identification of such environmental factors [7]; furthermore, if not taken into account in clinics and research, it may bias longitudinal assessment of disease activity both at individual and group level [8,9].

Unlike multiple sclerosis (MS), another immune-mediated, neuroinflammatory disease, wherein season of birth is a risk factor [10] and the incidence of relapses peaks in spring and early summer [8,11,12], it is unknown whether seasonal variation exists in AQP4-Ab disease and MOG-Ab disease. We therefore aimed to examine the seasonal distribution of attacks in AQP4-Ab disease and MOG-Ab disease, looking at both total attacks and onset events within each group.

Section snippets

Source of data

We used data from three centres in the United Kingdom: the Walton Centre (Liverpool), the University Hospital of Wales (Cardiff) and the John Radcliffe Hospital (Oxford). Patients followed up in these cohorts had their clinical data prospectively recorded on each centre's database. Anonymised data relevant for this study was then retrieved from the local databases using a structured form.

Population

We included AQP4-Ab-seropositive patients and MOG-Ab-seropositive patients where there were exact attack

Results

We included 244 patients with AQP4-Ab-positive disease and 98 patients with MOG-Ab disease, for whom a total of 1000 and 235 confirmed attacks, respectively, had been recorded, of which 905 and 216 attacks, respectively, had accurate start date at least to the month level. Of these, 194 attacks in the AQP4-Ab group and 81 attacks in the MOG-Ab group were onset events. Further demographic and clinical data are shown in Table 1.

Monthly frequencies of attacks in each group are shown in

Discussion

Seasonal patterns in autoimmune diseases can be mediated by a number of environmental factors. Several infections and some vaccines have been linked to autoimmune conditions, including ADEM [20,21]. Night length and exposure to ultraviolet radiation modulate the secretion of melatonin and vitamin D, which exert immunomodulatory functions in MS and other immune-mediated diseases [6]. Indeed, counts of immune cells and levels of cytokines and chemokines have been shown to vary according to the

Conclusion

There does not seem to be an important seasonal variation in AQP4-Ab disease attacks. A seasonal effect in MOG-Ab disease was not identified, but cannot be ruled out given the smaller sample size. In comparison to MS, these antibody-mediated diseases may be either less susceptible to environmental factors or susceptible to different ones with no seasonal variation.

The following are the supplementary data related to this article.

. (Supplemental). Distribution of attacks across the year. Histograms

Funding

No specific funding was needed for this study.

Ethics approval

All patients provided written consent to the use of their clinical data for research (Oxford Research Ethics Committee reference 16/SC/0224).

Consent to participate

Not applicable.

Consent for publication

Not applicable.

Availability of data and material

Not applicable.

Code availability

Not applicable.

Authors' contributions

Dr. dos Passos: conception of the work; data collection; data analysis and interpretation; drafting the article; critical revision of the article; final approval of the version to be published.

Dr. Elsone: conception of the work; data collection; data analysis and interpretation; drafting the article; critical revision of the article; final approval of the version to be published.

Dr. Luppe: data collection; critical revision of the article; final approval of the version to be published.

Dr.

Declaration of Competing Interest

Dr. dos Passos reports scholarships from the European Committee for Treatment and Research in MS, World Federation of Neurology and Novartis; funding for research from Biogen, Novartis and Roche; travel grants from Merck, Roche, Sanofi-Genzyme and Teva; fees for editorial content from Bayer, Merck Serono and Roche; and compensation for advisory work from Biogen.

Dr. Elsone reports honorarium from Teva for developing an educational material.

Dr. Luppe has nothing to disclose with regards to this

Acknowledgements

We are grateful to our colleagues providing the diagnostic assay for AQP4-Ab and MOG-Ab at the John Radcliffe Hospital (Angela Vincent, Patrick Waters and Mark Woodhall). We are also grateful to our Neurology and Ophthalmology colleagues across the UK for referring patients to the National Diagnostic and Advisory Service for Neuromyelitis Optica.

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Myelin injury without astrocytopathy in neuroinflammatory disorders with MOG antibodies
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Cited by (10)

Detecting seasonal trends in optic neuritis within the Ottawa region
2024, Canadian Journal of Ophthalmology
In this study we aim to determine seasonal patterns underlying optic neuritis (ON) onset that may provide valuable epidemiologic information and help delineate causative or protective factors.
Single-centre retrospective chart review.
A database search of centralized electronic health records was completed using diagnostic codes employed at the Ottawa Eye Institute for data collection. Charts were reviewed for documentation supporting a diagnosis of ON falling into the following categories: multiple sclerosis ON and clinically isolated syndrome ON, myelin oligodendrocyte glycoprotein ON, neuromyelitis optica ON, and idiopathic ON. Date of onset, biological sex, and age were extracted from each chart. Data were analyzed for calculation of frequency by season and overall pooled seasonal trends of all cases of ON.
From the 218 included patients with ON, there was no statistically significant seasonal correlation. The overall trend of ON was lowest in winter and spring (22% and 23%, respectively) and highest in summer and fall (28% and 27% respective). Divided further, multiple sclerosis ON or clinically isolated syndrome ON rates (n = 144) were lowest in the spring (21%) and highest in fall (29%); myelin oligodendrocyte glycoprotein ON rates (n = 25) were lowest in winter (16%) and highest in summer and fall (both at 32%); neuromyelitis optica ON rates (n = 16) were lowest in fall (12.5%) and highest in winter and summer (both at 31.25%); and idiopathic ON rates (n = 33) were lowest in fall (18%) and highest in spring (33%).
The overall ON seasonal trend appears to have a predilection for the summer and fall months, which may be explained by warmer weather and viral infections as risk factors for multiple sclerosis relapse during those seasons.
La présente étude avait pour objectif de déterminer le schéma saisonnier sous-tendant l'apparition de la névrite optique (NO) afin de faire ressortir de précieuses données épidémiologiques et de décrire les facteurs de causalité ou de protection.
Étude rétrospective des dossiers médicaux d'un établissement unique.
Nous avons eu recours aux codes de diagnostics utilisés à l'Institut de l’œil de l'Université d'Ottawa pour passer en revue la base de données des dossiers médicaux électroniques centralisés en vue de notre collecte de données. Les dossiers ont été dépouillés afin d'en extraire les données qui étayaient un diagnostic de NO en fonction des catégories suivantes: NO liée à la sclérose en plaques et à un événement inflammatoire monophasique avec démyélinisation (clinically isolated syndrome), NO liée à la glycoprotéine oligodendrocytaire de myéline, NO liée à la neuromyélite optique et NO idiopathique. La date d'apparition, le sexe biologique et l’âge des patients ont été vérifiés dans chaque dossier. On a procédé à une analyse des données afin de calculer la fréquence d'apparition de la NO en fonction des saisons et les tendances saisonnières globales colligées pour tous les cas de NO.
On ne note aucune corrélation saisonnière statistiquement significative chez les 218 porteurs de NO inclus dans l’étude. La tendance globale a permis de constater que le taux de NO était le plus faible en hiver et au printemps (22 % et 23 %, respectivement) et le plus élevé en été et en automne (28 % et 27 %, respectivement). Si l'on examine les données plus à fond, on note que le taux de NO liée à la sclérose en plaques ou à un événement inflammatoire monophasique avec démyélinisation (n = 144) était le plus faible au printemps (21 %) et le plus élevé en automne (29 %); le taux de NO liée à la glycoprotéine oligodendrocytaire de myéline (n = 25) était le plus faible en hiver (16 %) et le plus élevé en été et en automne (32 % dans les 2 cas); le taux de NO liée à la neuromyélite optique (n = 16) était le plus faible en automne (12,5 %) et le plus élevé en hiver et en été (31,25 % dans les 2 cas); enfin, le taux de NO idiopathique (n = 33) était le plus faible en automne (18 %) et le plus élevé au printemps (33 %).
D'après les tendances saisonnières globales en matière d'apparition de la NO, celle-ci semble se manifester surtout pendant les mois d’été et d'automne. Voilà qui pourrait s'expliquer par le fait que le temps chaud et les infections virales propres à l’été et à l'automne, respectivement, constituent des facteurs de risque de poussée de sclérose en plaques.
Prevalence, incidence, and season distribution of MOG antibody-associated disease in the province of Verona, Italy
2022, Multiple Sclerosis and Related Disorders
Citation Excerpt :
Among the incident cases that were included in the study, we spotted a predominance of disease onset for the autumn-winter period, in contrast with the spring peak of onset of MS. This finding is in line with a study conducted on MOGAD and AQP4-seropositive NMOSD in Japanese patients, in which the former showed a fall-winter predominance of clinical onset while the latter had a spring-summer peak of onset (Akaishi et al., 2020). However, another report from a UK cohort of MOGAD and AQP4 seropositive NMOSD patients showed no clear variation in disease onset and relapses (dos Passos et al., 2020). Hence, our observational data should be interpreted with caution, as the topic is still controversial and needs to be further investigated in larger studies.
Myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease (MOGAD) is a demyelinating disorder of the central nervous system whose epidemiological features are still unclear. We report current prevalence and incidence rates of MOGAD in the population of Verona province, Italy, and the seasonal distribution of disease onset.
MOGAD patients residing in Verona province were included through the consultation of a database from our Neuropathology Laboratory. Provincial prevalence was determined on 2021/1/1 (resident population: 922,291 people) and incidence rates between 2016/1/1 and 2021/1/1 were calculated from all cases, divided by the total number of person-years at risk. We also examined the distribution of attacks by month and season.
We included 23 prevalent MOGAD cases (13 females), with a median age at onset of 36 years (range 5–69). Prevalence rate was 2.5/100,000 (95% CI 1.7–3.7). 22 incident cases were collected, with an incidence rate of 4.8/million person-years (95% CI 3.1–7.2). Among the 23 prevalent patients, disease onset was more frequent in December (4 cases), February, May, and September (3 cases/month), with a global autumn-winter predominance (September-February) of 15 cases (65%), irrespective of the clinical manifestation.
This is the first study on an Italian population to report MOGAD prevalence and incidence rates; they are higher than the estimates for aquaporin-4-seropositive neuromyelitis optica spectrum disorder in the Caucasian population, but far lower than Multiple Sclerosis. An autumn-winter predominance of disease onset is suggested, and it could be related to environmental factors that should be ascertained, although validation in larger cohorts is mandatory.
Seasonal variation in attacks of neuromyelitis optica spectrum disorders and multiple sclerosis: Evaluation of 794 attacks from a nationwide registry in Argentina
2022, Multiple Sclerosis and Related Disorders
Citation Excerpt :
Some of these factors have been well described in autoimmune diseases like MS (Watad et al., 2017). Likewise, the presence of seasonal variation could help to find these environmental factors, particularly in NMOSD (Watad et al., 2017; Dos Passos et al., 2020; Kermode et al., 2020). Additionally, the identification of such factors should be considered in clinical practice as well as for clinical studies of both MS and NMOSD, as it might help in the identification of bias in the disease activity assessment during follow-up (Kermode et al., 2020).
Identification of triggers that potentially instigate attacks in neuromyelitis optica spectrum disorders (NMOSD) and multiple sclerosis (MS) has remained challenging. We aimed to analyze the seasonality of NMOSD and MS attacks in an Argentinean cohort seeking differences between the two disorders.
A retrospective study was conducted in a cohort of NMOSD and MS patients followed in specialized centers from Argentina and enrolled in RelevarEM, a nationwide, longitudinal, observational, non-mandatory registry of MS/NMOSD patients. Patients with complete relapse data (date, month and year) at onset and during follow-up were included. Attack counts were analyzed by month using a Poisson regression model with the median monthly attack count used as reference.
A total of 551 patients (431 MS and 120 NMOSD), experiencing 236 NMOSD-related attacks and 558 MS-related attacks were enrolled. The mean age at disease onset in NMOSD was 39.5 ± 5.8 vs. 31.2 ± 9.6 years in MS (p < 0.01). Mean follow-up time was 6.1 ± 3.0 vs. 7.4 ± 2.4 years (p < 0.01), respectively. Most of the included patients were female in both groups (79% vs. 60%, p < 0.01). We found a peak of number of attacks in June (NMOSD: 28 attacks (11.8%) vs MS: 33 attacks (5.9%), incidence rate ratio 1.82, 95%CI 1.15–2.12, p = 0.03), but no differences were found across the months in both disorders when evaluated separately. Strikingly, we observed a significant difference in the incidence rate ratio of attacks during the winter season when comparing NMOSD vs. MS (NMOSD: 75 attacks (31.7%) vs MS: 96 attacks (17.2%), incidence rate ratio 1.82, 95%CI 1.21–2.01, p = 0.02) after applying Poisson regression model. Similar results were observed when comparing the seropositive NMOSD (n = 75) subgroup vs. MS.
Lack of seasonal variation in MS and NMOSD attacks was observed when evaluated separately. Future epidemiological studies about the effect of different environmental factors on MS and NMOSD attacks should be evaluated prospectively in Latin America population.
Seasonal variation of onset in patients with anti-aquaporin-4 antibodies and anti-myelin oligodendrocyte glycoprotein antibody
2020, Journal of Neuroimmunology
Citation Excerpt :
Such indolent onset in MS may have obscured the seasonal variation in the clinical onset in the MS group in this study. A recent demographic study from the United Kingdom reported a lack of seasonal variation in attacks in AQP4-IgG or MOG-IgG-positive NMOSD (Dos Passos et al., 2020). A possible theory to explain the observed discrepancy between the seasonal variation in Asian countries (China and Japan) and the United Kingdom is the climate characteristics specific to East Asia.
This study aimed to determine the seasonal impact on the clinical onset of inflammatory neurological diseases of the central nervous system by analyzing the onset month with information on clinical manifestations in Japanese patients. As a result, patients with anti-aquaporin-4 antibodies (AQP4-IgG)-positive neuromyelitis optica spectrum disorders (NMOSD) showed spring–summer predominance of the clinical onset. Conversely, patients with anti-myelin oligodendrocyte glycoprotein antibody (MOG-IgG)-associated disease showed autumn–winter predominance of the clinical onset. Both seasonal variations were irrespective of the clinical manifestation. Environmental factors with seasonal variation influence the development of neurological conditions related to AQP4-IgG and MOG-IgG.
Seasonal variation in relapse of neuromyelitis optica spectrum disorders: A retrospective study in China
2020, Journal of Neuroimmunology
Citation Excerpt :
These inconsistencies may attribute to small sample size as well as insufficient follow-up time allowing us to observe enough relapses, intricated relationship between each climatic factor could also reduce the the effectiveness of t-test on our data. Some previous studies found no significant correlation between seasonality and relapse of NMOSD (Dos Passos et al., 2020, Muto, Mori, 2013) or multiple sclerosis (Fonseca et al., 2009). Our results support a recent study which also find seasonal bias for relapses in spring-summer in NMOSD (Khalilidehkordi et al., 2020).
Neuromyelitis optica spectrum disorder relapses and seasonal influence in an equatorial country cohort
2024, Revista de Neurologia

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¹: These authors contributed equally to this work.

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Seasonal distribution of attacks in aquaporin-4 antibody disease and myelin-oligodendrocyte antibody disease

Highlights

Abstract

Background

Objective

Methods

Results

Conclusion

Introduction

Section snippets

Source of data

Population

Results

Discussion

Conclusion

Funding

Ethics approval

Consent to participate

Consent for publication

Availability of data and material

Code availability

Authors' contributions

Declaration of Competing Interest

Acknowledgements

J. Autoimmun.

J. Neurol. Sci.

J. Neuroimmunol.

Distinction between MOG antibodypositive and AQP4 antibody-positive NMO spectrum disorders

Neurology

Neuromyelitis optica spectrum disorders with aquaporin-4 and myelin-oligodendrocyte glycoprotein antibodies: a comparative study

JAMA Neurol.

Seizures and encephalitis in myelin oligodendrocyte glycoprotein IgG disease vs aquaporin 4 IgG disease

JAMA Neurol.

Neuromyelitis optica should be classified as an astrocytopathic disease rather than a demyelinating disease

Clin. Exp. Neuroimmunol.

Myelin injury without astrocytopathy in neuroinflammatory disorders with MOG antibodies

J. Neurol. Neurosurg. Psychiatry

Finding causes of seasonal diseases using time series analysis

Int. J. Epidemiol.

Seasonal variation in multiple sclerosis relapse

J. Neurol.

Seasonal prevalence of MS disease activity

Neurology

Time- and region-specific season of birth effects in multiple sclerosis in the United Kingdom

JAMA Neurol.

Seasonal variation of relapse rate in multiple sclerosis is latitude dependent

Ann. Neurol.

Multicentre comparison of a diagnostic assay: aquaporin-4 antibodies in neuromyelitis optica

J. Neurol. Neurosurg. Psychiatry

The recognition and estimation of cyclic trends

Ann. Hum. Genet.