MS and Disability Progression in Latin America, Africa, Asia and the Middle East: A Systematic Review

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Highlights

  • MS phenotypes and outcomes in previously understudied world regions are systematically reviewed

  • Stratification of neuromyelitis optica spectrum disorder has allowed for more appropriate comparison of traditional MS in Asia and other countries.

  • The clinical phenotypes and disability progression of MS in Latin America, Africa, Asia and the Middle East-North Africa region have similarities to Western MS.

Abstract

Background

There is evidence of an increased prevalence and disease burden of Multiple Sclerosis (MS) in parts of the world where the risk was once considered low, such as Latin America (LA), Sub-Saharan Africa, Asia and the Middle East-North Africa (MENA). Despite the growing number of clinical reports, the phenotype and course of MS in these regions remains understudied compared with Europe and North America. We aimed to investigate MS phenotypes and long-term clinical outcomes across these regions.

Method

A Boolean search of the medical literature was conducted between January 1980 and April 30, 2020. PubMed, SCOPUS, Global Health, and the Cochrane databases, were used to identify all relevant citations. Articles were collated and managed on Covidence® software. We independently appraised the articles for meeting study criteria and for quality using the Critical Appraisal Skills Program (CASP) and the Specialist Unit for Review Evidence (SURE) system.

Results

A total of 1,639 studies were imported for screening. After removing 545 duplicates, two authors assessed 1,094 abstracts and selected 515 for full-text screening. 72 articles met study criteria, including 19 studies from LA, 4 from sub-Saharan Africa, 24 from Asia and 25 from MENA. The overall sex ratio was 2.5:1 (female: male). Disability was assessed using the Expanded Disability Status Scale (EDSS). Longitudinal disability progression and time to standard endpoints was compared by region and with relevant Western reports. Patients with MS living in the MENA region appear to reach disability milestones faster than those in the Western world, although this finding is not uniform. South Asia shows distinct disability features compared with East Asia, more closely resembling those of the West. Disease morbidity in East Asia appears more benign than in the West after careful exclusion of neuromyelitis optica spectrum disorder cases. Populations in LA tend to have similar MS features to the Western world, but some exceptions exist, including African descendants that reach disability milestones earlier. Using all studies with appropriate survival analysis, the mean time to EDSS 6.0 was 16.97 years with a heterogeneity index of 24.59.

Conclusion

The clinical phenotypes and disability progression of MS in LA, Africa, Asia and the MENA region have similarities to Western MS. In some regions and subpopulations there is evidence of a more aggressive course, possibly due to a combination of genetic and environmental factors. More population-based longitudinal data are needed, particularly in Sub-Saharan Africa.

Introduction

There is evidence of an increased prevalence and disease burden of Multiple Sclerosis (MS) in parts of the world where the risk was once considered low including: Latin America (LA), Middle East-North Africa (MENA), Sub-Saharan Africa and Asia (GBD 2016 Multiple Sclerosis Collaborators, 2019). The Global Burden of Disease (GBD) 2016 study group assessed percentage change in age-standardized Disability Adjusted Life Years related to MS between 1990 and 2016. Some of the largest increases in disability were seen in non-Western regions: Central LA: 37.3%; MENA: 16.1%; Sub-Saharan Africa: 11.0%; and South Asia: 19.4%. Age at onset, race and opticospinal MS (OSMS) presentation were identified as factors influencing progression in the clinical course of MS.

Regarding race, some reports showed that MS tends to be diagnosed earlier and is more aggressive among African Americans compared to Caucasians in the United States, reaching neurological disability levels more rapidly (Cree et al., 2004; Buchanan et al., 2004). Shifting to Europe, a study showed that people with MS (PwMS) living in France and of North African (NA) origin had more severe disability progression than French Caucasians (Debouverie et al., 2007).

In Eastern Asia, optico-spinal MS (OSMS) was proposed to be classified as ‘Asian-type MS’ (Kira et al., 1996), a disease with different clinical, radiological and immunological features compared to the so called ‘Western-type’ conventional MS (CMS). People with OSMS were found to reach disability milestones faster than their CMS counterparts, but also showed higher age at onset, a female sex preponderance, lower number of brain lesions and lower frequency of oligoclonal bands (OCBs) in the CSF (Kira J, 2003). OSMS had also been diagnosed in Southern Asia (Wasay et al., 2007), frequently in the MENA region (Yaqub, 1988) and less frequently in LA (Lana-Peixoto, 2008).

More recently, the discovery of anti-aquaporin 4 (AQP4) antibodies and the introduction of new diagnostic criteria for neuromyelitis optica (NMO) allowed the separation of OSMS into true MS cases with opticospinal presentation and cases belonging to the NMO spectrum (Wingerchuk et al., 2006). However, the debate on this topic is still active and many features of MS epidemiology in those regions where OSMS was more prevalent require a reassessment to better understand the MS phenotype.

Over the last two decades, many epidemiological studies have been performed in the majority world where the disease was historically less common. The purpose of the present review is to highlight the existing data on the MS clinical phenotypes and long-term morbidity in LA, Asia, Sub-saharan Africa and the MENA region.

Section snippets

Methods

A comprehensive literature review was conducted using several online databases including PubMed, SCOPUS, Global Health, and the Cochrane database from January 1st, 1980 to April 30th, 2020. A Boolean search was conducted using the same principles and terms between searches. All searches contained a variant of the following search terms: “Multiple Sclerosis AND (Phenotype OR Progression OR Disability OR Morbidity OR Longitudinal OR Expanded Disability Status Scale (EDSS) OR Clinical outcome OR

Results

We identified 1,604 peer-reviewed articles in our search of databases, then 35 additional studies from other sources. The search was narrowed to 1,094 unique articles once duplicates were removed and 579 of these were excluded after the first screening (Figure 1). A total of 515 articles were assessed full text for eligibility and 443 were excluded for: irrelevancy, wrong design, limited disease duration, small or non-MS patient sample, or foreign language. A total of 72 studies met the

Discussion

Our review of the long-term morbidity of MS in regions where the disease has been historically less studied has shown that the MS phenotype and progression is similar to the experience in Europe and North America. Our analysis reveals that MS can be defined by standardized criteria, and neurological disease progression is variable as assessed by MRI lesions and clinical morbidity outcomes.

We selected a few relevant studies on long-term MS morbidity from Western countries to allow comparison

Conclusion

The phenotype and disability progression of MS in LA, MENA, Asia and Sub-Saharan Africa have similarities to Western MS but in several regions take on a more aggressive course. MS progression is most rapid in MENA and selected LA regions where there are a high percentage of PwMS of African descent. Studies in Asia show mild to moderate progression when NMOSD cases are excluded from MS cohorts. In this region, the application of updated diagnostic criteria (Wingerchuck et al., 2015) and the

Declaration of Conflicting Interests

The authors declared no potential conflicts of interest with respect to the research, authorship, or publication of this article.

Funding

This study was funded in part by the VA MS Center of Excellence-East. We are grateful to Elaine Sullo and the Himmelfarb Medical Library staff for their assistance on our review and development of the Covidence database. We also acknowledge the collaboration of Ho Kim, MD, PhD (Head, Department of Neurology, research Institute and Hospital, National Cancer Institute, Goyand, Korea) who provided additional data and assisted with data interpretation of the epidemiology of MS in Asia.

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