Abstract
Background: Multiple sclerosis is the most common inflammatory neurological disease in young adults. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) provides a systematic method of quantifying various effects of a given condition by demographic variables and geography. In this systematic analysis, we quantified the global burden of multiple sclerosis and its relationship with country development level. Methods: We assessed the epidemiology of multiple sclerosis from 1990 to 2016. Epidemiological outcomes for multiple sclerosis were modelled with DisMod-MR version 2.1, a Bayesian meta-regression framework widely used in GBD epidemiological modelling. Assessment of multiple sclerosis as the cause of death was based on 13 110 site-years of vital registration data analysed in the GBD's cause of death ensemble modelling module, which is designed to choose the optimum combination of mathematical models and predictive covariates based on out-of-sample predictive validity testing. Data on prevalence and deaths are summarised in the indicator, disability-adjusted life-years (DALYs), which was calculated as the sum of years of life lost (YLLs) and years of life lived with a disability. We used the Socio-demographic Index, a composite indicator of income per person, years of education, and fertility, to assess relations with development level. Findings: In 2016, there were 2 221 188 prevalent cases of multiple sclerosis (95% uncertainty interval [UI] 2 033 866–2 436 858) globally, which corresponded to a 10·4% (9·1 to 11·8) increase in the age-standardised prevalence since 1990. The highest age-standardised multiple sclerosis prevalence estimates per 100 000 population were in high-income North America (164·6, 95% UI, 153·2 to 177·1), western Europe (127·0, 115·4 to 139·6), and Australasia (91·1, 81·5 to 101·7), and the lowest were in eastern sub-Saharan Africa (3·3, 2·9–3·8), central sub-Saharan African (2·8, 2·4 to 3·1), and Oceania (2·0, 1·71 to 2·29). There were 18 932 deaths due to multiple sclerosis (95% UI 16 577 to 21 033) and 1 151 478 DALYs (968 605 to 1 345 776) due to multiple sclerosis in 2016. Globally, age-standardised death rates decreased significantly (change −11·5%, 95% UI −35·4 to −4·7), whereas the change in age-standardised DALYs was not significant (−4·2%, −16·4 to 0·8). YLLs due to premature death were greatest in the sixth decade of life (22·05, 95% UI 19·08 to 25·34). Changes in age-standardised DALYs assessed with the Socio-demographic Index between 1990 and 2016 were variable. Interpretation: Multiple sclerosis is not common but is a potentially severe cause of neurological disability throughout adult life. Prevalence has increased substantially in many regions since 1990. These findings will be useful for resource allocation and planning in health services. Many regions worldwide have few or no epidemiological data on multiple sclerosis, and more studies are needed to make more accurate estimates. Funding: Bill & Melinda Gates Foundation.
| Original language | English |
|---|---|
| Pages (from-to) | 269-285 |
| Number of pages | 17 |
| Journal | The Lancet Neurology |
| Volume | 18 |
| Issue number | 3 |
| DOIs | |
| Publication status | Published - Mar 2019 |
Access to Document
Other files and links
Fingerprint
Dive into the research topics of 'Global, regional, and national burden of multiple sclerosis 1990–2016: a systematic analysis for the Global Burden of Disease Study 2016'. Together they form a unique fingerprint.Cite this
- APA
- Author
- BIBTEX
- Harvard
- Standard
- RIS
- Vancouver
}
In: The Lancet Neurology, Vol. 18, No. 3, 03.2019, p. 269-285.
Research output: Contribution to journal › Article › peer-review
TY - JOUR
T1 - Global, regional, and national burden of multiple sclerosis 1990–2016
T2 - a systematic analysis for the Global Burden of Disease Study 2016
AU - GBD 2016 Multiple Sclerosis Collaborators
AU - Wallin, Mitchell T.
AU - Culpepper, William J.
AU - Nichols, Emma
AU - Bhutta, Zulfiqar A.
AU - Gebrehiwot, Tsegaye Tewelde
AU - Hay, Simon I.
AU - Khalil, Ibrahim A.
AU - Krohn, Kristopher J.
AU - Liang, Xiaofeng
AU - Naghavi, Mohsen
AU - Mokdad, Ali H.
AU - Nixon, Molly R.
AU - Reiner, Robert C.
AU - Sartorius, Benn
AU - Smith, Mari
AU - Topor-Madry, Roman
AU - Werdecker, Andrea
AU - Vos, Theo
AU - Feigin, Valery L.
AU - Murray, Christopher J.L.
N1 - Funding Information: With the rigorous standardised GBD approach for morbidity assessments, we estimated that there were around 2·2 million cases of multiple sclerosis worldwide in 2016. In that year, prevalence was 10·4% higher than in 1990. Multiple sclerosis also contributed 0·04% (95% UI 0·04–0·05) of total DALYs and 0·05% (0·04–0·07) of all YLLs in 2016. Although neurological disability progression is variable, DALYs peaked in the sixth decade of life. Because onset is most frequently in early adulthood and because survival has been improved, people with multiple sclerosis are affected throughout adult life, leading to the high number of YLDs. The disability weights for multiple sclerosis are generally high ( appendix ) and YLDs begin to increase steeply early in the second decade of life. We found a strong latitude gradient for the prevalence of multiple sclerosis, with an increase in prevalence of 1·03 times per degree of latitude. A north to south decrease in prevalence by latitude gradient has been recognised in North America and western Europe, 28,29 and a reverse south to north increase in gradient has been reported in Australia. 28 Temporal trends in prevalence show that these gradients were weakening in the 20th century, 9 but the distribution of multiple sclerosis can still be generally described as having three zones of frequency or risk ( figure 1 ), as originally proposed by Kurtzke. 30 In 2016, northern European countries and North America made up the high-risk prevalence zone, with estimates of 100 or more cases of multiple sclerosis per 100 000 population. These regions are bounded by areas of medium frequency (prevalence 30–100 cases per 100 000). Low-frequency areas are centred around the equator, and the prevalence in Asia is less than 30 cases per 100 000 population. Geographical location before onset of multiple sclerosis remains a risk factor for acquisition. 28 Clear gradients from low to high prevalence between low and high SDI quintiles are reported on the GBD 2016 website. The burden of multiple sclerosis was greatest in the regions with the highest socioeconomic status. These gradients point to environmental risk factors that modulate risk based on location. Prevalence of multiple sclerosis differed substantially over the adult life of women and men. Rising multiple sclerosis morbidity among women in the later 20th century has been reported in studies of multiple sclerosis prevalence and incidence. 7,30 An analysis of data from the Danish Multiple Sclerosis Registry showed that incidence in women doubled between 1950 and 2009, whereas increases among men have been more modest. 31 By contrast, excess mortality among patients with multiple sclerosis in Denmark has declined since 1950. 32 Environmental changes that might be contributing to the rapid change in incidence among women include the rise in obesity, increased cigarette smoking, and changes in the frequency of breastfeeding infants. 31,33 Our results are consistent with some previous reports of multiple sclerosis morbidity from around the world. Canadian studies have indicated the highest multiple sclerosis prevalence estimates so far. In the province of British Columbia, prevalence was 179·9 cases per 100 000 population in 2008. 34 This value is close to our estimate for all of Canada, which fell into the band of 150–180 cases per 100 000 population. However, an estimate of 266·9 cases per 100 000 population in Nova Scotia from 2010 35 is substantially higher. The prevalence of multiple sclerosis reported from European regions has been variable, with values being higher in northern than in southern regions. For example, national prevalence of 154·5 cases per 100 000 was reported in Denmark in 2005, 36 and an estimate of 230·6 cases per 100 000 population in Northern Ireland was reported in 2008. 37 A meta-analysis suggests prevalence below 100 cases per 100 000 population in France and southern and eastern Europe. 6 Studies of multiple sclerosis prevalence in South America have largely been done in small regions, but a study from Panama produced a national crude prevalence of 5·2 per 100 000, 38 which is notably lower than the estimates for North America. Studies in Africa have been sparse and those from Asia have had variable quality. 39 Nevertheless, our world map of multiple sclerosis prevalence is similar to the 2013 MS International Federation world atlas for multiple sclerosis morbidity by country and region. 10 Incidence of multiple sclerosis has been relatively stable or slightly increased over the past four to five decades in white populations, but has been higher in selected racial groups. 7–9 Therefore, the rising prevalence estimates for multiple sclerosis across high-income regions and countries might mostly reflect improved survival. 40 In addition, the diagnostic criteria for multiple sclerosis have evolved and earlier diagnosis is possible with the use of neuroimaging, and these factors are likely to be contributing to the increased prevalence observed. 41 Genetic susceptibility to multiple sclerosis is an important factor that influences risk for onset. 3 Multiple sclerosis is considered to be a complex genetic disease, with over 200 alleles having been discovered to contribute small risk effects. 3 Yet the rapid changes by sex, race, and ethnicity in incidence and prevalence over the past few generations give support to environmental factors as drivers of susceptibility to multiple sclerosis. 9 Prime candidates include infection, such as with the Epstein-Barr virus or other organisms, as the initiator of multiple sclerosis, 42 with the suggestion that infections start in the gut and spread to the CNS. 42,43 Environmental exposures, such as smoking, 44 lack of sunlight, 45 diet, 46 changes in the gut microbiome, 47 and obesity, 48 have also received support as risk factors for onset of multiple sclerosis. The GBD 2016 neurological data related to multiple sclerosis provide a pathway for priority setting and service planning in health care in relation to other disorders. The rising cost of multiple sclerosis disease-modifying medications is a major global concern. 49 Ensuring access to disease-modifying medications as well as rehabilitation and multidisciplinary care will help to slow disability progression and support independence in daily activities for patients with multiple sclerosis. Ageing of the large multiple sclerosis population in North America and Europe will be important for health-care providers and policy makers to assess patients' future health-service needs. 50 Ways to provide adaptive work environments and cost-effective nursing care options to patients will be important for policy planners in regions where prevalence is increasing. The GBD methods have limitations for the epidemiological assessment of multiple sclerosis. First, data are absent or extremely sparse for many regions of the world, including Latin America, sub-Saharan Africa, and Asia. As such, the models we used to predict prevalence, DALYs, and YLLs might lead to unusual changes in segments of the data. For example, the rapid increases in prevalence in women older than 80 years and the YLD curve we estimated should be viewed with caution because they are not typical of individual population-based studies. We cannot exclude that the relatively low burden of multiple sclerosis in less-developed countries was related to the underdiagnosis of the condition due to limited access to specialised medical care, imaging resources, and laboratory investigations. Additionally, even in high-income regions where multiple sclerosis is well studied, there are few national prevalence and incidence studies, and case-ascertainment infrastructures are limited. For example, in Greenland our estimate for multiple sclerosis prevalence was based on one study in a small community of fewer than 2000 inhabitants, in which no cases of multiple sclerosis were found between 1950 and 1974. 51 The uncertainty around this mean incidence value of 0 per 100 000 incidence is so wide that it is compatible with a high prevalence, as predicted by our latitude covariate. We acknowledge that with additional epidemiological data this high estimate for Greenland might be altered, but until such information becomes available we maintain that the results from our model are valid. A second major limitation was the lack of robust predictive covariates for multiple sclerosis to aid in population-based risk assessments, 24 which was due partly to the limited pool of longitudinal neurological disability data that is representative of the multiple sclerosis population. We found a significant relationships between multiple sclerosis, prevalence, latitude, level of development. However, by including both covariates we might have underestimated the effect of latitude because of collinearity between SDI and distance from the equator. Inclusion of SDI as a covariate might also have spuriously led to increasing estimates of prevalence over time. Latitude remains a proxy and, therefore, an uncertain predictor for multiple sclerosis as long as there is no established biological basis for the relationship. With sparse data and uncertain predictive covariates, we cannot exclude that some of the variation measured in prevalence is due to measurement error. One way forward for the assessment of the global burden of multiple sclerosis is to use a validated algorithm approach to estimate prevalence and incidence in population-based health care administrative datasets. 52 This approach has been successfully applied to North American multiple sclerosis populations. 40,52 The availability of medical claims data from the USA makes us more confident of the estimates for that country. GBD is actively seeking access to medical claims data in other countries to improve the accuracy of estimates for diseases such as multiple sclerosis, for which every patient can be expected to be in contact with the health-care system if there are no major barriers to accessing care. Through our network of collaborators, we expect future iterations of GBD to be able to add such sources from other countries. In summary, multiple sclerosis is an important cause of neurological disability throughout adult life. This report gives an integrated, contemporary understanding of the global multiple sclerosis disease burden. Prevalence has increased partly due to improved survival. The GBD approach to estimating multiple sclerosis morbidity and mortality is novel and can be repeated with relative efficiency. Our findings will be useful for resource allocation and health services planning for the growing numbers of patients with multiple sclerosis in ageing societies. More national multiple sclerosis epidemiological studies, especially from low-income and middle-income countries, are needed for the GBD Multiple Sclerosis collaborators to generate robust worldwide estimates in the future. GBD 2016 Multiple Sclerosis Collaborators Mitchell T Wallin, William J Culpepper, Emma Nichols, Zulfiqar A Bhutta, Tsegaye Tewelde Gebrehiwot, Simon I Hay, Ibrahim A Khalil, Kristopher J Krohn, Xiaofeng Liang, Mohsen Naghavi, Ali H Mokdad, Molly R Nixon, Robert C Reiner, Benn Sartorius, Mari Smith, Roman Topor-Madry, Andrea Werdecker, Theo Vos, Valery L Feigin, and Christopher J L Murray. Affiliations Department of Neurology, George Washington University, Washington, DC, USA (M T Wallin MD); VA Multiple Sclerosis Center of Excellence, Department of Neurology, University of Maryland School of Medicine, Baltimore, MD, USA (M T Wallin, W J Culpepper PhD); Institute for Health Metrics and Evaluation, University of Washington, Seattle, WA, USA (E Nichols BA, Prof S I Hay DSc, I A Khalil MD, K J Krohn MPH, Prof M Naghavi PhD, Prof A H Mokdad PhD, M R Nixon PhD, R C Reiner PhD, M Smith MPA, Prof T Vos PhD, Prof V L Feigin PhD, Prof C J L Murray DPhil); Centre for Global Child Health, University of Toronto, Toronto, ON, Canada (Prof Z A Bhutta PhD); Center of Excellence in Women and Child Health, Aga Khan University, Karachi, Pakistan (Prof Z A Bhutta); Department of Epidemiology, Jimma University, Jimma, Ethiopia (T T Gebrehiwot MPH); Chinese Center for Disease Control and Prevention, Beijing, China (Prof X Liang MD); Department of Public Health Medicine, University of KwaZulu-Natal, Durban, South Africa (Prof B Sartorius PhD); Institute of Public Health, Jagiellonian University Medical College, Krakow, Poland (R Topor-Madry PhD); Agency for Health Technology Assessment and Tariff System, Warszawa, Poland (R Topor-Madry); Demographic Change and Ageing Research Area, Federal Institute for Population Research, Wiesbaden, Germany (A Werdecker PhD); Staufenberg, Germany (A Werdecker); and National Institute for Stroke and Applied Neurosciences, Auckland University of Technology, Auckland, New Zealand (Prof V L Feigin). Contributors MTW and WJC prepared the first draft. EN, TV, and VLF analysed the data and edited the first and final drafts of the Article. MTW and WJC finalised all drafts and approved the final version of the manuscript. All other authors provided data, developed models, reviewed results, provided guidance on methodology, or reviewed the manuscript, and approved the final version of the Article. Declaration of interests We declare that we have no competing interests. Publisher Copyright: © 2019 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license
PY - 2019/3
Y1 - 2019/3
N2 - Background: Multiple sclerosis is the most common inflammatory neurological disease in young adults. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) provides a systematic method of quantifying various effects of a given condition by demographic variables and geography. In this systematic analysis, we quantified the global burden of multiple sclerosis and its relationship with country development level. Methods: We assessed the epidemiology of multiple sclerosis from 1990 to 2016. Epidemiological outcomes for multiple sclerosis were modelled with DisMod-MR version 2.1, a Bayesian meta-regression framework widely used in GBD epidemiological modelling. Assessment of multiple sclerosis as the cause of death was based on 13 110 site-years of vital registration data analysed in the GBD's cause of death ensemble modelling module, which is designed to choose the optimum combination of mathematical models and predictive covariates based on out-of-sample predictive validity testing. Data on prevalence and deaths are summarised in the indicator, disability-adjusted life-years (DALYs), which was calculated as the sum of years of life lost (YLLs) and years of life lived with a disability. We used the Socio-demographic Index, a composite indicator of income per person, years of education, and fertility, to assess relations with development level. Findings: In 2016, there were 2 221 188 prevalent cases of multiple sclerosis (95% uncertainty interval [UI] 2 033 866–2 436 858) globally, which corresponded to a 10·4% (9·1 to 11·8) increase in the age-standardised prevalence since 1990. The highest age-standardised multiple sclerosis prevalence estimates per 100 000 population were in high-income North America (164·6, 95% UI, 153·2 to 177·1), western Europe (127·0, 115·4 to 139·6), and Australasia (91·1, 81·5 to 101·7), and the lowest were in eastern sub-Saharan Africa (3·3, 2·9–3·8), central sub-Saharan African (2·8, 2·4 to 3·1), and Oceania (2·0, 1·71 to 2·29). There were 18 932 deaths due to multiple sclerosis (95% UI 16 577 to 21 033) and 1 151 478 DALYs (968 605 to 1 345 776) due to multiple sclerosis in 2016. Globally, age-standardised death rates decreased significantly (change −11·5%, 95% UI −35·4 to −4·7), whereas the change in age-standardised DALYs was not significant (−4·2%, −16·4 to 0·8). YLLs due to premature death were greatest in the sixth decade of life (22·05, 95% UI 19·08 to 25·34). Changes in age-standardised DALYs assessed with the Socio-demographic Index between 1990 and 2016 were variable. Interpretation: Multiple sclerosis is not common but is a potentially severe cause of neurological disability throughout adult life. Prevalence has increased substantially in many regions since 1990. These findings will be useful for resource allocation and planning in health services. Many regions worldwide have few or no epidemiological data on multiple sclerosis, and more studies are needed to make more accurate estimates. Funding: Bill & Melinda Gates Foundation.
AB - Background: Multiple sclerosis is the most common inflammatory neurological disease in young adults. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) provides a systematic method of quantifying various effects of a given condition by demographic variables and geography. In this systematic analysis, we quantified the global burden of multiple sclerosis and its relationship with country development level. Methods: We assessed the epidemiology of multiple sclerosis from 1990 to 2016. Epidemiological outcomes for multiple sclerosis were modelled with DisMod-MR version 2.1, a Bayesian meta-regression framework widely used in GBD epidemiological modelling. Assessment of multiple sclerosis as the cause of death was based on 13 110 site-years of vital registration data analysed in the GBD's cause of death ensemble modelling module, which is designed to choose the optimum combination of mathematical models and predictive covariates based on out-of-sample predictive validity testing. Data on prevalence and deaths are summarised in the indicator, disability-adjusted life-years (DALYs), which was calculated as the sum of years of life lost (YLLs) and years of life lived with a disability. We used the Socio-demographic Index, a composite indicator of income per person, years of education, and fertility, to assess relations with development level. Findings: In 2016, there were 2 221 188 prevalent cases of multiple sclerosis (95% uncertainty interval [UI] 2 033 866–2 436 858) globally, which corresponded to a 10·4% (9·1 to 11·8) increase in the age-standardised prevalence since 1990. The highest age-standardised multiple sclerosis prevalence estimates per 100 000 population were in high-income North America (164·6, 95% UI, 153·2 to 177·1), western Europe (127·0, 115·4 to 139·6), and Australasia (91·1, 81·5 to 101·7), and the lowest were in eastern sub-Saharan Africa (3·3, 2·9–3·8), central sub-Saharan African (2·8, 2·4 to 3·1), and Oceania (2·0, 1·71 to 2·29). There were 18 932 deaths due to multiple sclerosis (95% UI 16 577 to 21 033) and 1 151 478 DALYs (968 605 to 1 345 776) due to multiple sclerosis in 2016. Globally, age-standardised death rates decreased significantly (change −11·5%, 95% UI −35·4 to −4·7), whereas the change in age-standardised DALYs was not significant (−4·2%, −16·4 to 0·8). YLLs due to premature death were greatest in the sixth decade of life (22·05, 95% UI 19·08 to 25·34). Changes in age-standardised DALYs assessed with the Socio-demographic Index between 1990 and 2016 were variable. Interpretation: Multiple sclerosis is not common but is a potentially severe cause of neurological disability throughout adult life. Prevalence has increased substantially in many regions since 1990. These findings will be useful for resource allocation and planning in health services. Many regions worldwide have few or no epidemiological data on multiple sclerosis, and more studies are needed to make more accurate estimates. Funding: Bill & Melinda Gates Foundation.
UR - http://www.scopus.com/inward/record.url?scp=85061307617&partnerID=8YFLogxK
U2 - 10.1016/S1474-4422(18)30443-5
DO - 10.1016/S1474-4422(18)30443-5
M3 - Article
C2 - 30679040
AN - SCOPUS:85061307617
SN - 1474-4422
VL - 18
SP - 269
EP - 285
JO - The Lancet Neurology
JF - The Lancet Neurology
IS - 3
ER -