Global Prevalence and Incidence of Amyotrophic Lateral Sclerosis: A Systematic Review

Abstract

Background and objectives: Amyotrophic lateral sclerosis (ALS) is a rare neurodegenerative disorder affecting upper and lower motor neurons. Due to its rarity and rapidly progressive nature, studying the epidemiology of ALS is challenging, and a comprehensive picture of the global burden of this disease is lacking. The objective of this systematic review was to describe the global incidence and prevalence of ALS.

Methods: We searched MEDLINE, Embase, Global Health, PsycInfo, Cochrane Library, and CINAHL to identify articles published between January 1, 2010, and May 6, 2021. Studies that were population based and reported estimates of prevalence, incidence, and/or mortality of ALS were eligible for inclusion. This study focuses on the incidence and prevalence. Quality assessment was performed using a tool developed to evaluate methodology relevant to prevalence and incidence studies. This review was registered with PROSPERO, CRD42021250559.

Results: This search generated 6,238 articles, of which 140 were selected for data extraction and quality assessment. Of these, 85 articles reported on the incidence and 61 on the prevalence of ALS. Incidence ranged from 0.26 per 100,000 person-years in Ecuador to 23.46 per 100,000 person-years in Japan. Point prevalence ranged from 1.57 per 100,000 in Iran to 11.80 per 100,000 in the United States. Many articles identified cases with ALS from multiple data sources.

Discussion: There is variation in reported incidence and prevalence estimates of ALS across the world. While registries are an important and powerful tool to quantify disease burden, such resources are not available everywhere. This results in gaps in reporting of the global epidemiology of ALS, as highlighted by the degree of variation (and quality) in estimates of incidence and prevalence reported in this review.

Figure 1. Study Selection Flowchart

These totals include studies that reported on ALS mortality/survival. ALS = amyotrophic lateral sclerosis; PRISMA = Preferred Reporting Items for Systematic Reviews and Meta-Analyses.

Figure 2. Distribution of QA Scores for Studies Reporting Incidence Only, Prevalence Only, or Both, Stratified by Continent

QA scores were obtained by dividing the numerator (i.e., number of questions answered “yes”) by the denominator (i.e., total number of applicable questions for the study). The maximum attainable score for a study that assessed 1 parameter (incidence, prevalence or mortality/survival) was 9. If the study assessed 2 parameters, the maximum attainable score was 11, and if all 3 parameters were assessed the maximum attainable score was 13. The greater the score (i.e., the closer the ratio of the numerator and denominator is to 1), the greater the quality of the study based on the parameters evaluated in the QA tool. QA = quality assessment.

Figure 3. Crude Incidence Reported per Study, Stratified by Continent

*Adjusted incidence estimate. Excluded studies: Incidence of 23.46 per 100,000 person-years in Oshima, Japan (Kihira et al., 2012).^e1 Study conducted by Palese et al. (2019) is a continuation (extended study period, same methods) of a study conducted by Drigo et al. (2013), and we included only the most recent study by Palese et al. (2019) in Figures 3 and 4.^e2,e3 Similarly, Kab et al. (2017) and Ahmadzai et al. (2018) presented identical ALS incidence estimates in France, with overlapping study periods and identical data sources; thus, we included only the study conducted by Ahmadzai et al. (2018) in Figures 3 and 4.^e4,e5 Govoni et al. (2012 and 2015) presented updated estimates in their most recent study (inclusion of 1 additional incident case over the same study period); for this reason, only study conducted by Govoni et al. (2015) is included in Figures 3 and 4.^e6,e7 Two studies from Ireland (Rooney et al., 2014; Tobin et al., 2016) were omitted from Figures 3 and 4 because they did not report incidence rates (they reported measures of relative risk of ALS); these 2 studies are nevertheless summarized in eTable 1 (links.lww.com/WNL/C896).^e8,e9 One study (Vucic et al., 2020) reported incidence rates for Japan, South Korea, and Australia; however, the incidence of ALS in Australia was derived from mortality data and not estimated directly, so it was not included in Figures 3 and 4 for Oceania.^e10 One study from the United Kingdom used data from the UK Million Women Study, and the estimate provided in Figure 3 is an incidence rate per 100,000 women-years (originally presented per 1,000).^e11 ALS = amyotrophic lateral sclerosis.

Figure 4. Overall Median Incidence and per Continent

Excluded studies: incidence of 23.46 per 100,000 person-years in Oshima, Japan (Kihira et al., 2012).^e1 Palese et al. (2019) is a continuation (extended study period, same methods) of a study conducted by Drigo et al. (2013), and we included only the most recent study by Palese et al. (2019) in Figures 3 and 4.^e2,e3 Similarly, Kab et al. (2017) and Ahmadzai et al. (2018) presented identical ALS incidence estimates in France, with overlapping study periods and identical data sources; thus, we include only the study conducted by Ahmadzai et al. (2018) in Figures 3 and 4.^e4,e5 Govoni et al. (2012 and 2015) presented updated estimates in their most recent study (inclusion of 1 additional incident case over the same study period); for this reason, only the study conducted by Govoni et al. (2015) is included in Figures 3 and 4.^e6,e7 Two studies from Ireland (Rooney et al., 2014; Tobin et al., 2016) were omitted from Figures 3 and 4 because they did not report incidence rates (they reported measures of relative risk of ALS); these 2 studies are, nevertheless, summarized in eTable 1 (links.lww.com/WNL/C896).^e8,e9 One study (Vucic et al., 2020) reported incidence rates for Japan, South Korea, and Australia; however, the incidence of ALS in Australia was derived from mortality data and not estimated directly, so it was not included in Figures 3 and 4 for Oceania.^e10 ALS = amyotrophic lateral sclerosis.

Figure 5. Crude Prevalence Reported per study, Stratified by Continent

Point prevalence date/ period is noted in each study's respective bar. *Adjusted prevalence estimate. Excluded studies: Point prevalence for a study from Indonesia (Okumiya et al., 2014) reported extreme values with point estimates of 73.00 (95% CI 0–156) per 100,000 and 133.00 (95% CI 27–240) per 100,000.^e85 Mansukhani et al. (2018) in Gujarat, India (8,537 individuals from 1,464 households across 3 villages) reported a prevalence of 109.53 (no CI included) per 100,000 for upper motor neuron disease and 1,010.10 per 100,000 for lower motor neuron disease.^e86 One study from the Faroe Islands (Johansen et al., 2020) reported a period prevalence over a 20-year period (1987–2016) of 122.50 per 100,000 inhabitants (original estimate was presented per 1,000).^e87 Rosenbohm et al. (2017) did not estimate prevalence directly but used estimated mean survival and estimated incidence to derive an estimate of prevalence.^e66 Conde et al. (2019) used riluzole consumption as a proxy for ALS diagnosis (with no other measures of validation); this study was also excluded.^e88 Wittie et al. (2014) reported a period prevalence of 38.50 per 100,000 over a 5-year period, 2001–2005, in Georgia, United States.^e89 Bhattacharya et al. (2019) reported a 5-year (2007–2011) period prevalence of 20.50 per 100,000.^e90 Sagiraju et al. (2020) reported a prevalence of 19.70 per 100,000 over a period of more than a decade (2001–2015) among the post-9/11 Veteran population in the United States.^e91 ALS = amyotrophic lateral sclerosis.

Figure 6. Overall Median (1-Year Period and Point) Prevalence and per Continent

For studies reporting a period prevalence of greater than 1-year interval (n = 11), 1-year prevalence was computed. Excluded studies: point prevalence for a study from Indonesia (Okumiya et al., 2014) reported extreme values with point estimates of 73.00 (95% CI 0–156) per 100,000 and 133.00 (95% CI 27–240) per 100,000.^e85 Mansukhani et al. (2018) in Gujarat, India (8,537 individuals from 1,464 households across 3 villages) reported a prevalence of 109.53 (no CI included) per 100,000 for upper motor neuron disease and 1,010.10 per 100,000 for lower motor neuron disease.^e86 Rosenbohm et al. (2017) did not estimate prevalence directly but used estimated mean survival and estimated incidence to derive an estimate of prevalence.^e66 Conde et al. (2019) used riluzole consumption as a proxy for ALS diagnosis (with no other measures of validation); this study was also excluded.^e88 ALS = amyotrophic lateral sclerosis.