Highlights
- •Trends in MS incidence rates over time have not been examined on a global basis.
- •Our systematic review included 65 regional estimates across 24 countries.
- •By absolute number of studies, the predominant pattern was increasing MS incidence.
- •No pattern was seen with consistent case definitions/high population coverage.
- •There were few eligible studies to assess change in incidence in many regions.
Abstract
Background
Methods
Results
Conclusion
Keywords
Abbreviations:
MS (Multiple sclerosis)1. Introduction
The Multiple Sclerosis International Federation (MSIF). Atlas of MS, 3rd Edition: Mapping multiple sclerosis around the world key epidemiology findings, 2020, https://www.msif.org/wp-content/uploads/2020/10/Atlas-3rd-Edition-Epidemiology-report-EN-updated-30-9-20.pdf.
- Cortese R.
- Collorone S.
- Ciccarelli O.
- Toosy AT.
The Multiple Sclerosis International Federation (MSIF). Atlas of MS, 3rd Edition: Mapping multiple sclerosis around the world key epidemiology findings, 2020, https://www.msif.org/wp-content/uploads/2020/10/Atlas-3rd-Edition-Epidemiology-report-EN-updated-30-9-20.pdf.
2. Methods
2.1 Search strategy and selection criteria
- Moher D.
- Liberati A.
- Tetzlaff J.
- Altman D.G.
- Group P.
2.2 Study inclusion criteria
2.3 Identification of studies
2.4. Data extraction and quality assessment
The Multiple Sclerosis International Federation (MSIF). Atlas of MS, 3rd Edition: Mapping multiple sclerosis around the world key epidemiology findings, 2020, https://www.msif.org/wp-content/uploads/2020/10/Atlas-3rd-Edition-Epidemiology-report-EN-updated-30-9-20.pdf.
Wells G., Shea B., O'Connell D., Peterson J., Welch V., Losos M., et al. (2020) The Newcastle-Ottawa Scale (NOS) for assessing the quality of nonrandomised studies in meta-analysis [10 October 2020]. Available from: http://www.ohri.ca/programs/clinical_epidemiology/oxford.asp.
2.5. Analysis
3. Results
The Multiple Sclerosis International Federation (MSIF). Atlas of MS, 3rd Edition: Mapping multiple sclerosis around the world key epidemiology findings, 2020, https://www.msif.org/wp-content/uploads/2020/10/Atlas-3rd-Edition-Epidemiology-report-EN-updated-30-9-20.pdf.
- Nicoletti A.
- Rascuna C.
- Boumediene F.
- Vasta R.
- Cicero C.E.
- Lo Fermo S.
- et al.
- Flemmen H.O.
- Simonsen C.S.
- Berg-Hansen P.
- Moen S.M.
- Kersten H.
- Heldal K.
- et al.
Primary author, year of publication; location | Case definition or diagnostic criteria | Case ascertainment data source | Time period; calendar years | Mean annual incidence per 100,000 population during period (95% CI provided where available) | Absolute annual change estimate (95% CI) p value | Incidence trend | |
Crude | Standardised | ||||||
Americas Region | |||||||
Al-Sakran 201819 Saskatchewan, Canada | ‘Marrie algorithm’: ≥3 hospital, physician, or MS DMD claims (prescriptions filled) ( Marrie et al., 2010 )‘CCDSS algorithm’: ≥1 hospital or ≥5 physician claims within 2 years ICD-9/10 codes 340/G35 | Province-wide health administrative data, including hospital, physician and prescription claims | 2004–2008 | NR | 18.84 (Marrie algorithm) 16.23 (CCDSS) | –0.76 (-1.21, -0.30) p=0.005 (Marrie algorithm) -0.89 (-1.21, -0.56) p<0.001 (CCDSS) | Incidence decreased Marrie algorithm (2004–2013) |
2009–2013 | NR | 14.43 (Marrie algorithm) 11.78 (CCDSS) | Incidence decreased CCDSS (2004–2013) | ||||
Hader 200721 Saskatoon, Saskatchewan, Canada | Allison and Millar, 1954; Schumacher; Poser | Regional hospital records, family physicians, neurologists, nursing homes, Home Care Program, MS Society and a provincial MS Treatment Database (est. 1997) | 1990–1999 | 9.20 (7.90–10.70) | NR | -0.12 (-0.16, -0.07) p<0.001 | Incidence decreased (1990–2004) |
2000–2004 | 7.90 (6.20–9.90) | NR | |||||
Kingwell 201522 British Columbia, Canada | ≥ 7 MS claims (ICD-9/10 codes 340/G35) for people who were resident in British Columbia for >3 years following the first MS or demyelinating disease claim; ≥ 3 MS claims for those with ≤ 3 years of residency (akin to the Marrie algorithm) | Health administrative data, including hospital, physician and prescriptions filled | 1999–2003 | 8.28 | 8.18 | -0.12 (-0.36, 0.12) p=0.29 | Incidence stable (1999–2008) |
2004–2008 | 7.52 | 7.36 | |||||
Marrie 201323 Nova Scotia, Canada | ≥ 7 MS claims (ICD-9/10 codes 340/G35) for people with >3 years of administrative data; ≥ 3 MS claims for those with ≤ 3 years of data (akin to the Marrie algorithm) | Health administrative data including hospital, physician claims and MS clinic data | 1996–2000 | NR | 11.44 | -0.34 (-0.56, -0.12) p=0.005 | Incidence decreased (1995–2010) |
2001–2005 | NR | 10.13 | |||||
2006–2010 | NR | 8.30 | |||||
Rotstein 201824 Ontario, Canada | ≥1 hospital or ≥5 physician claims for MS (ICD-9/10 codes 340/G35) within 2 years; (restricted to: ≥20 years); akin to the CCDSS algorithm | Province-wide health administrative data including hospital and physician claims | 1999–2003 | NR | 16.20 | -0.24 (-0.51, 0.03) p=0.08 | Incidence stable |
2004–2008 | NR | 14.37 | (1999–2013) | ||||
2009–2013 | NR | 14.47 | |||||
Widdifield 201525 Ontario, Canada | ≥1 hospital or ≥5 physician claims for MS (ICD-9/10 codes 340/G35) within 2 years; (restricted to: ≥20 years); akin to the CCDSS algorithm | Province-wide health administrative data including hospital and physician claims | 2001–2005 | 15.30 | 15.00 | 0.15 (-0.40, 0.71) p=0.55 | Incidence stable |
2006–2010 | 15.14 | 15.62 | (2001–2010) | ||||
Sloka 200526 Newfoundland and Labrador, Canada | Poser | Hospital records; 8 of the 9 practicing neurologists; regional MS clinic/MS registry | 1987–1991 | 18.47 | NR | 1.00 (0.29, 1.71) p=0.009 | Incidence increased |
1992–1996 | 26.76 | NR | (1987–2001) | ||||
1997–2001 | 28.33 | NR | |||||
Warren 200827 Alberta, Canada | ≥1 hospital or ≥2 physician claims for MS (ICD-9 code 340) | Province-wide health administrative data including hospital and physician claims | 1990–1994 | NR | 20.80 | 0.25 (0.09, 0.41) p=0.005 | Incidence increased |
1995–1999 | NR | 22.66 | (1990–2004) | ||||
2000–2004 | NR | 23.30 | |||||
Cabre 200928 French West Indies (Martinique and Guadeloupe) | McDonald 2005 | Inflammatory CNS diseases registry (1992–2007) based on: hospital records, open-care neurologists, health records, health insurance organisations, MS patient associations | July1992-June1997 | 0.93 (0.76–1.20) | NR | 0.07 (0.05, 0.08) p<0.001 | Incidence increased (1992–2006) |
July1997-June2002 | 1.20 (1.01–1.39) | NR | |||||
July2002-June2007 | 1.67 (1.46–1.88) | NR | |||||
Gracia 200929 Republic of Panama | Poser; McDonald 2001 (used from 2003) | Clinical files from the National Public Health System and private practice | 1991–1995 | 0.20 | NR | 0.02 (0.01, 0.35) p=0.006 | Incidence increased |
1996–2000 | 0.34 | NR | (1991–2005) | ||||
2001–2005 | 0.42 | NR | |||||
Europe Region | |||||||
Joensen 201130 Faroe Islands | Poser (applied from 1943–1986); Poser, McDonald and Thompson (used 1986–2007) | Hospital records, government disability registry, private neurologist | 1993–2002 | 4.90 (2.90–7.00) | NR | -0.22 (-0.32, -0.13) p<0.001 | Incidence decreased (1993–2007) |
2003–2007 | 2.40 (2.10–3.30) | NR | |||||
Koch-Henriksen 201831 Denmark | Allison and Millar, 1954 (for MS onset before 1994); Poser (for MS onset 1994–2004); McDonald (for MS onset 2005-end); (initially all ages, then restricted to: 10–64 years) | Danish MS Registry | 1990–1999 | Female 11.33 (10.93–11.75) Male 5.65 (5.37–5.95) | 8.29 (8.05–8.54) | 0.09 (0.06, 0.11) p<0.001 | Incidence increased (1990–2009) |
2000–2009 | Female 12.33 (11.91–12.75) Male 6.08 (5.79–6.38) | 9.43 (9.17–9.69) | |||||
Krökki 201132 Northern Ostrobothnia, Northern Finland | Poser; McDonald 2001 | Hospital records | 1993–1997 | 4.55 | NR | 0.26 (0.07, 0.46) p=0.01 | Incidence increased |
1998–2002 | 7.15 | NR | (1993–2007) | ||||
2003–2007 | 7.46 | NR | |||||
Sarasoja 200433 Central Finland (4 districts) | Poser | Hospital records | 1989–1993 | 3.68 (2.30–5.10) | NR | 0.84 (0.45, 1.22) p=0.001 | Incidence increased (1989–1998) |
1994–1998 | 9.20 (7.40–10.90) | NR | |||||
Benedikz 200234 Iceland | Poser | Nationwide survey of MS (hospital records) | 1986–1990 | 5.28 | NR | -0.36 (-0.44, -0.28) p<0.001 | Incidence decreased (1986–2000) |
1991–1995 | 3.71 | NR | |||||
1996–2000 | 1.28 | NR | |||||
Benjaminsen 201435 Nordland County, Norway | Poser; McDonald (used from 2001) | Hospitals records | 1985–1989 | 5.00 (3.80–6.40) | 5.40 | 0.25 (0.20, 0.29) p<0.001 | Incidence increased (1985–2009) |
1990–1994 | 5.30 (4.04–6.72) | 5.40 | |||||
1995–1999 | 7.20 (5.73–8.85) | 7.30 | |||||
2000–2004 | 7.40 (5.94–9.12) | 7.60 | |||||
2005–2009 | 10.10 (8.36–12.98) | 10.70 | |||||
Celius 200136 Oslo, Norway | Poser | Oslo MS-Registry including hospital records, patient registries, private neurologists, MS rehabilitation and nursing homes, patient societies, disability pension records from the National Health Insurance Administration | 1987–1991 | 7.20 (5.00–10.20) | NR | 0.23 (0.12, 0.33) p=0.001 | Incidence increased (1987–1996) |
1992–1996 | 8.70 (6.30–11.90) | NR | |||||
Dahl 200437 Nord-Trøndelag County, Norway | Poser | Hospitals, outpatient clinic and the sole private neurologist records | 1989–1993 | 4.70 (3.20–6.70) | 5.10 | 0.08 (0.04, 0.11) p=0.001 | Incidence increased (1989–1998) |
1994–1998 | 5.30 (3.70–7.50) | 5.60 | |||||
Flemmen 202038 Telemark County, Norway | ICD-10 code G35 (1999–2019) and fulfilled McDonald criteria 2010, 2017 Or ICD-9 code 340 (1993–1998) with a ‘verified MS diagnosis’ (criteria NR) | BOT-MS project database (records from 2 regional hospitals and majority of MS patients at Oslo University Hospital) | 1999–2003 | 8.20 (3.90–12.60) | 8.40 (4.00–12.80) | 0.33 (0.25, 0.41) p<0.001 | Incidence increased (1999–2018) |
2004–2008 | 11.80 (6.60–17.00) | 11.80 (6.60–17.10) | |||||
2009–2013 | 11.10 (6.10–16.10) | 11.30 (6.20–16.30) | |||||
2014–2018 | 13.90 (8.30–19.50) | 14.40 (8.70–20.00) | |||||
Grytten 201639 Hordaland County, Western Norway | Poser (used through to 2002); McDonald 2010 (used from 2003 onwards) | Hospital records; All patients referred from GPs and private neurologists | 1988–1992 | 7.52 | NR | -0.09 (-0.15, -0.04) p=0.002 | Incidence decreased |
1993–1997 | 8.39 | NR | (1988–2012) | ||||
1998–2002 | 6.82 | NR | |||||
2003–2007 | 8.19 | NR | |||||
2008–2012 | 5.24 | NR | |||||
Lund 201440 Vestfold County, Norway | Poser (used from 1983–2002); also classified by McAlpine for comparison with other studies (used from 1953–1982) | Hospital records, private neurologists, nursing homes, a rehabilitation institute, National MS Registry | 1988–1992 | 6.05 | NR | -0.16 (-0.22, -0.10) p<0.001 | Incidence decreased |
1993–1997 | 4.34 | NR | (1988–2002) | ||||
1998–2002 | 4.24 | NR | |||||
Risberg 201141 Oppland County, Norway | Poser | Hospitals and GP records | 1989–1993 | 6.50 (4.90–8.30) | 6.60 | 0.15 (0.08, 0.22) p=0.001 | Incidence increased (1989–1998) |
1994–1998 | 7.40 (5.80–9.40) | 7.60 | |||||
Simonsen 201742 Buskerud County, Norway | Poser (before 2001); McDonald 2001, 2005, 2010 (after 2001) | Hospital and private neurology records | 2003–2007 | 10.20 | NR | 0.44 (0.24, 0.64) p=0.001 | Incidence increased |
2008–2012 | 13.10 | NR | (2003–2012) | ||||
Vatne 201143 Vest-Agder County, Norway | Poser | Hospital and neurological specialist records | 1996–2000 (5 years) | 7.20 | 7.50 (4.20–13.50) | 0.07 (0.04, 0.10) p=0.001 | Incidence increased |
2001–2006 (6 years) | 7.50 | 8.00 (4.60–14.20) | (1996–2006) | ||||
Willumsen 202044 Møre and Romsdal County, Norway | Allison and Millar, 1954; McAlpine; Schumacher; Poser; McDonald 2001, 2005, 2010, 2017 | Data from previously published studies (1950–1991), 2 unpublished master's theses (presented in 2009 and 2011), subsequent years: hospital records and outpatient clinics | 1985–1989 | 7.00 (5.60–8.60) | 7.60 | 0.29 (0.23, 0.35) p<0.001 | Incidence increased (1985–2014) |
1990–1994 | 9.40 (7.80–11.40) | 9.70 | |||||
1995–1999 | 7.50 (6.10–9.20) | 7.80 | |||||
2000–2004 | 12.50 (10.60–14.70) | 12.90 | |||||
2005–2009 | 13.70 (11.70–15.90) | 14.30 | |||||
2010–2014 | 13.60 (11.70–15.80) | 14.20 | |||||
Boström 200945 Värmland County, Western Sweden | Poser | Hospital records, the sole private neurologist, larger health care centers | 1991–1995 | 6.46 (5.14–7.78) | NR | -0.01 (-0.02, -0.01) p=0.001 | Incidence decreased (1991–2000) |
1996–2000 | 6.39 (5.06–7.72) | NR | |||||
Svenningsson 201546 Västerbotten County, North Sweden | Poser (used before 2002); McDonald 2005, 2010 (used from 2002 onwards); Used ICD-8/9/10 code for MS | Swedish MS registry and national health administrative data, including hospital and outpatients | 1991–1995 | 5.66 | NR | 0.09 (-0.02, 0.21) p=0.11 | Incidence stable |
1996–2000 | 4.56 | NR | (1991–2010) | ||||
2001–2005 | 5.77 | NR | |||||
2006–2010 | 6.96 | NR | |||||
Vrabec-Matković 200647 Bjelovar-Bilogora County, Croatia | Poser | Hospital records, MS Society registry | 1987–1991 | 1.94 | NR | 0.04 (0.03, 0.06) p<0.001 | Incidence increased |
1992–1996 | 2.36 | NR | (1987–2001) | ||||
1997–2001 | 2.40 | NR | |||||
Klupka-Sarić 200748 Western Herzegovina, Bosnia-Herzegovina | McDonald 2001 | Hospital records, regional medical centre, outpatient services | 1994–1998 | 1.6 (0.00–3.30) | NR | 0.05 (-0.15, 0.24) p=0.61 | Incidence stable (1994–2003) |
1999–2003 | 1.7 (0.00–3.40) | NR | |||||
Debouverie 200749 Lorraine, France | Poser | Lorraine MS Regional Network of neurologists (hospital records, MS centres, neurologists records, other healthcare professionals and MS Association) | 1993–1997 | 5.33 | NR | 0.19 (0.04, 0.35) p=0.02 | Incidence increased |
1998–2002 | 6.45 | NR | (1993–2002) | ||||
Daltrozzo 201850 Bavaria, Germany | ICD-10 code G35: in at least two separate quarterly periods, not necessarily the same year | Ambulatory claims data | 2006–2010 | 17.18 | 16.70 | 0.01 (-0.18, 0.20) p=0.91 | Incidence stable |
2011–2015 | 17.40 | 17.01 | (2006–2015) | ||||
Kotzamani 201251 Crete, Greece | McDonald 2001, 2005 | MS Epidemiology Program Project of Crete (including major medical centres of Crete) | 1985–1989 | Female 3.50 Male 1.70 | NR | 0.18 (0.15, 0.22) p<0.001 (Male) 0.23 (0.20, 0.27) p<0.001 (Female) | Incidence increased Male and Female |
1990–1994 | Female 4.10 Male 2.40 | NR | (1985–2004) | ||||
1995–1999 | Female 5.70 Male 4.10 | NR | |||||
2000–2004 | Female 7.10 Male 4.30 | NR | |||||
Papathanasopoulos 200852 Western Greece, Prefectures of Aitolokarnania, Achaia and Ilia, Greece | Poser; McDonald 2001, 2005 | Hospital clinic records | 1987–1991 | 2.99 | 3.24 | 0.47 (0.27, 0.66) p<0.001 | Incidence increased |
1992–1996 | 7.01 | 7.53 | (1987–2006) | ||||
1997–2001 | 6.91 | 7.54 | |||||
2002–2006 | 10.08 | 10.74 | |||||
Piperidou 200353 Province of Evros, North-Eastern Greece | Poser | Hospital records, outpatient clinic, private neurologists, Greek MS Association | 1989–1993 | 2.09 (1.17–3.44) | NR | -0.01 (-0.15, 0.13) p=0.87 | Incidence stable (1989–1999) |
1994–1999 | 2.36 (1.44–3.65) | NR | |||||
Cocco 201154 South-Western part of Sardinia, Italy | McDonald 2001, 2005 | Two MS referral centres, rehabilitation centres | 1988–1997 | NR | 5.94 | 0.16 (0.11, 0.21) p<0.001 | Incidence increased |
1998–2007 | NR | 8.07 | (1988–2007) | ||||
Granieri 200055 Province of Nuoro, Sardinia, Italy | Allison and Millar, 1954; Schumacher; Poser | Hospital records, neurologists records, health records, National Pension Institute and National Health Insurance Scheme, MS Association | 1985–1989 | 6.60 (5.30–8.10) | NR | -0.03 (-0.04, -0.02) p<0.001 | Incidence decreased (1985–1995) |
1990–1995 | 6.40 (5.25–7.80) | NR | |||||
Granieri 200756 Province of Ferrara, Emilia-Romagna Region, North-eastern Italy | Poser | Hospitals, MS Centers, healthcare records, National Health Insurance Scheme, Italian MS Association, Telephone Surveys with health professionals | 1990–1994 | 3.44 | 3.40 | 0.14 (0.07, 0.20) p=0.001 | Incidence increased |
1995–1999 | 4.15 | 4.30 | (1990–1999) | ||||
Grassivaro 201957 Province of Padua (Padova), Northeast Italy | McDonald 2001, 2005 | Neurological centres, drug-dispensing records, outpatient records of neurorehabilitation services, chronic care services, local branch of the Italian Society for MS, archives of the National Pension Institute and National Health Insurance | 1990–1999 | 4.10 | NR | 0.12 (0.10, 0.13) p<0.001 | Incidence increased (1990–2015) |
2000–2009 | 5.50 | NR | |||||
2011–2015 | 6.50 | NR | |||||
Nicoletti 201158 City of Catania, Sicily, Italy | Poser | Neurological departments, Italian MS Association and clinical records | 1985–1989 | 2.30 (1.60–3.10) | 2.20 | 0.29 (0.25, 0.33) p<0.001 | Incidence increased (1985–2004) |
1990–1994 | 3.90 (3.00–5.00) | 3.90 | |||||
1995–1999 | 5.50 (4.40–6.70) | 5.70 | |||||
2000–2004 | 7.00 (4.30–10.20) | 6.80 | |||||
Nicoletti 201359 Mount Etna Regions, Catania, Sicily, Italy | Poser | Hospitals, MS Centers and Italian MS Association | 1990–1999 Western Flank | 4.20 | 3.70 | 0.02 (0.01, 0.02) p<0.001 (Western Flank) 0.04 (0.03, 0.05) p<0.001 (Eastern Flank) | Incidence increased Western and Eastern Flank |
2000–2009 Western Flank | 4.40 | 3.90 | (1990–2009) | ||||
1990–1999 Eastern Flank | 5.50 | 5.10 | |||||
2000–2009 Eastern Flank | 6.40 | 5.60 | |||||
Nicoletti 202060 Province of Catania, Sicily, Italy | McDonald 2001 | Neurological divisions and MS Centers of Catania | 2005–2010 | 8.70 (7.97–9.42) | NR | -0.15 (-0.22, -0.08) p=0.001 | Incidence decreased (2005–2015) |
2011–2015 | 7.60 (6.86–8.32) | NR | |||||
Patti 201961 City of Biancavilla, Catania, Sicily, Italy | Assessed separately using McDonald criteria 2001 and 2017 | Standardised database management system used by the main MS Centers in Italy | 1992–1996 | 6.30 (2001 criteria) 4.50 (2017 criteria) | NR | 0.55 (0.48, 0.63) p<0.001 (2001 criteria) 0.51 (0.43, 0.59) <0.001 (2017 criteria) | Incidence increased 2001 and 2017 criteria (1992–2018) |
1997–2001 | 7.10 (2001 criteria) 10.70 (2017 criteria) | NR | |||||
2002–2006 | 8.80 (2001 criteria) 9.60 (2017 criteria) | NR | |||||
2007–2011 | 14.50 (2001 criteria) 13.60 (2017 criteria) | NR | |||||
2012–2018 | 17.40 (2001 criteria) 16.80 (2017 criteria) | NR | |||||
Pugliatti 200162 Province of Sassari, Northern Sardinia, Italy | Poser | Hospital records, neurological clinic, private neurologists, GPs National MS Society | 1988–1992 | 6.20 (5.30–7.30) | NR | 0.09 (0.05, 0.13) p=0.001 | Incidence increased (1988–1997) |
1993–1997 | 6.80 (5.80–7.90) | NR | |||||
Pugliatti 200563 Province of Sassari, Northern Sardinia, Italy | Poser | MS registry | 1985–1989 | 6.50 (5.40–7.60) | 6.00 | -0.02 (-0.3, -0.00) p=0.01 | Incidence decreased (1985–1999) |
1990–1994 | 6.50 (5.40–7.60) | 6.10 | |||||
1995–1999 | 6.10 (5.10–7.20) | 5.80 | |||||
Ranzato 200364 Province of Padova (Padua), Northeast Italy | Poser | Hospital records, health records, Association if Invaliding Disease of Padova, National Pension Institute and National Health Insurance Scheme, Italian MS Society | 1985–1989 | 2.60 (2.08–3.12) | NR | 0.14 (0.01, 0.19) p<0.001 | Incidence increased (1985–1999) |
1990–1994 | 3.90 (3.19–4.61) | NR | |||||
1995–1999 | 4.20 (3.74–4.66) | NR | |||||
Salemi 200065 Bagheria City, Palermo, Sicily, Italy | Poser | Hospital records, out-patient neurology clinic, GPs & neurologists were ‘informed’, rehabilitation archives, public & private MRI centres, Office for Handicapped People, social workers, television channel | 1985–1989 | 3.50 (1.50–6.90) | NR | 0.27 (0.15, 0.40) p=0.001 | Incidence increased (1985–1994) |
1990–1994 | 5.30 (2.70–9.20) | NR | |||||
Solaro 201566 Province of Genoa, Italy | Poser | Hospital records, regionally serving neurologists, health records, disability pension records, Italian MS Society | 1998–2002 | 6.82 | NR | -0.05 (-0.34, 0.25) p=0.72 | Incidence stable |
2003–2007 | 6.26 | NR | (1998–2007) | ||||
Granieri 200867 Republic of San Marino | Poser | Hospital records (private & public), telephone surveys of neurologists, ophthalmologists, GPs, pharmacists, social workers | 1990–1994 | 10.80 (6.00–19.00) | NR | -0.32 (-0.49, -0.15) p=0.001 | Incidence decreased (1990–2005) |
1995–1999 | 6.20 (2.80–12.60) | NR | |||||
2000–2005 | 6.80 (3.20–11.40) | NR | |||||
1999–2003 | 1.7 (0.00–3.40) | NR | |||||
Valadkeviciene 201868 Lithuania | ICD-10 code G35: newly diagnosed MS in ambulatory service | Compulsory Health Insurance System including ambulatory and stationary visits | 2001–2005 | 5.48 | 5.36 | 0.47 (0.32, 0.63) p<0.001 | Incidence increased |
2006–2010 | 6.62 | 6.42 | (2001–2015) | ||||
2011–2015 | 9.85 | 9.69 | |||||
Kramer 201269 Netherlands | International Classification for Primary Care (records for more than 400 GPs in the Netherlands) | Integrated Primary Care Information database (a GP research database) | 1999–2003 | 3.97 | NR | 0.61 (0.15, 1.06) p=0.02 | Incidence increased |
2004–2008 | 6.67 | NR | (1999–2008) | ||||
Izquierdo 201570 Northern Seville District of Andalucia, Southern Spain | Poser | Hospital records, public and private neurologists | 1991–2000 | Female 4.30 (3.60–4.90) Male 2.50 (2.00–2.90) | NR | 0.36 (0.17, 0.54) p=0.001 (Female) -0.00 (-0.12, 0.11) p=0.96 (Male) | Incidence increased Female (1991–2010) |
2001–2010 | Female 8.80 (7.84–9.69) Male 2.80 (2.30–3.40) | NR | Incidence increased Male (1991–2010) | ||||
Modrego 200371 Bajo Aragon, Teruel, Central-Eastern Spain | Poser (used from 1994–2002); criteria not specified (1984–1993) | Hospital (inpatient and outpatient) records | 1988–1992 | 3.20 | NR | 0.05 (-0.40, 0.51) p=0.81 | Incidence stable (1988–2002) |
1993–1997 | 5.01 | NR | |||||
1998–2002 | 4.37 | NR | |||||
Hirst 200972 Cardiff, South East Wales, United Kingdom | Poser; McDonald 2001 | Hospital records, GP notifications, consultant neurologists | 1988–1992 | 4.90 | NR | 0.28 (0.22, 0.34) p<0.001 | Incidence increased |
1993–1997 | 5.70 | NR | (1988–2007) | ||||
1998–2002 | 7.15 | NR | |||||
2003–2007 | 8.75 | NR | |||||
Mackenzie 201473 United Kingdom | General Practice Research Database Read codes for confirmed diagnosis of MS beginning with F20 | General Practice Research Database, hospital records | 1991–1995 | Female 13.95 Male 6.69 | NR | -0.11 (-0.21, -0.00) p=0.05 (Female) -0.12 (-0.20, -0.05) p=0.004 (Male) | Incidence decreased (1991–2010) |
1996–2000 | Female 13.23 Male 6.07 | NR | Female Incidence decreased (1991–2010) | ||||
2001–2005 | Female 13.26 Male 5.26 | NR | Male | ||||
2006–2010 | Female 12.14 Male 4.99 | NR | |||||
Eastern Mediterranean Region | |||||||
Cheraghmakani 202074 Mazandaran Province, Northern Iran | McDonald 2001 | Provincial MS Society (‘collaborates with Mazandaran University of Medical Sciences, Neurology Association and other healthcare organisations’) | 2009–2013 | 5.48 | 4.64 | 0.08 (-0.09, 0.24) p=0.31 | Incidence stable |
2014–2018 | 5.80 | 4.98 | (2009–2018) | ||||
Elhami 201175 Tehran, Northern Iran | Poser (used up to 2001); McDonald 2001, 2005 | National MS Society (‘works in close cooperation with government; Iranian Neurological Association encourages neurologists to refer to the society’) | 1989–1993 | 1.01 | 1.00 | 0.20 (0.16, 0.25) p<0.001 | Incidence increased |
1994–1998 | 2.35 | 2.21 | (1989–2008) | ||||
1999–2003 | 4.02 | 3.49 | |||||
2004–2008 | 5.08 | 4.09 | |||||
Izadi 201576 Fars Province, Southern Iran | McDonald 2010 | MS centre referred by neurologists, Fars MS Society | 2003–2007 | 3.42 | NR | 0.87 (0.64, 1.09) p<0.001 | Incidence increased |
2008–2012 | 7.73 | NR | (2003–2012) | ||||
Mohebi 201977 Tehran, Iran | McDonald 2001 | MS Society | 1992–1996 | 2.48 | 0.18 (0.08, 0.28) p=0.001 | Incidence increased | |
1997–2001 | 4.20 | (1992–2016) | |||||
2002–2006 | 6.45 | ||||||
2007–2011 | 7.49 | ||||||
2012–2016 | 5.52 | ||||||
Western Pacific Region | |||||||
Ribbons 201778 Newcastle, Australia | Poser; McDonald 2010 | Public & private neurologists, private GPs, hospital discharge records and MS outpatient clinic database | 1986–1996 | 2.44 | 2.44 (1.68–3.47) | 0.24 (0.19, 0.29) p<0.001 | Incidence increased |
2001–2011 | 6.70 | 6.70 (5.39–8.01) | (1986–2011) | ||||
Houzen 201879 Tokachi Province, Hokkaido, Northern Japan | Poser | MS-related institutions (inpatient and outpatient clinical records) | 1985–1989 | 0.22 (0.06–0.56) | NR | 0.02 (0.01, 0.02) p<0.001 | Incidence increased (1985–2014) |
1990–1994 | 0.45 (0.19–0.89) | NR | |||||
1995–1999 | 0.61 (0.30–1.29) | NR | |||||
2000–2004 | 0.72 (0.38–1.23) | NR | |||||
2005–2009 | 0.79 (0.43–1.33) | NR | |||||
2010–2014 | 0.68 (0.35–1.19) | NR | |||||
Fang 202080 Taiwan | ≥1 hospital or ≥3 outpatient claims (ICD-9 codes 340) within 2 years | National Health Insurance Research Database | 2006–2010 | 1.63 | 1.47 | 0.01 (-0.02, 0.04) p=0.38 | Incidence stable |
2011–2015 | 1.69 | 1.52 | (2006–2015) | ||||
Paediatric-only studies | |||||||
Marrie 201818 Ontario, Canada | Marrie algorithm ≥3 hospital or physician claims for MS (ICD-9/10 codes 340/G35) CCDSS algorithm ≥1 hospital or ≥5 physician claims (ICD-9/10 codes 340/G35) within 2 years; (restricted to: 0–18 years) | Province-wide health administrative including hospital and physician claims | 2005–2009 | NR | 1.68 (Marrie algorithm) 1.17 (CCDSS) | -0.012 (-0.13, 0.10) p=0.81 (Marrie algorithm) -0.002 (-0.10, 0.10) p=0.97 (CCDSS) | Incidence stable Marrie algorithm (2005–2013) |
2010–2014 | NR | 1.57 (Marrie algorithm) 1.01 (CCDSS) | Incidence stable CCDSS (2005–2013) | ||||
Boesen 201881 Denmark | Allison and Millar, 1954 (used until 1994); Poser (used 1994–2004); McDonald (used from 2005); (restricted to: <18 years) | Danish MS Registry (all Danish departments of neurology contribute) | 1986–1990 | Female 0.94 Male 0.46 | NR | 0.009 (-0.02,0.35) p=0.47 (Female) -0.002 (-0.02, 0.01) p=0.79 (Male) | Incidence stable (1986–2015) |
1991–1995 | Female 1.36 Male 0.59 | NR | |||||
1996–2000 | Female 1.65 Male 0.63 | NR | |||||
2001–2005 | Female 1.28 Male 0.57 | NR | |||||
2006–2010 | Female 1.58 Male 0.43 | NR | |||||
2011–2015 | Female 1.14 Male 0.44 | NR | |||||
Alroughani 201582 Kuwait | IPMSSG consensus definition 2007 ( Krupp et al., 2007 ) (restricted to: <18 years at MS onset) | Kuwait National MS Registry (hospital and MS clinic databases) | 1994–1998 | 0.66 | NR | 0.07 (0.03, 0.10) p=0.001 | Incidence increased |
1999–2003 | 1.29 | NR | (1994–2013) | ||||
2004–2008 | 1.45 | NR | |||||
2009–2013 | 1.77 | NR |
3.1 Whole-of-population studies
Broad study location (number of studies); total general underlying population, plus calendar year; percentage of country's population covered by the study | Regional study location [population] | Total number incident MS cases/ total time period in years (study calendar years and other relevant detail) | Average annual number of cases | Approximate proportion of total country population covered by regional study |
Americas Region | ||||
Canada (8) Total Canada population 2000=30,736,000 2001=31,081,887 Approximate proportion of total (unique) country population covered by regional studies in Canada=69% | Saskatchewan ( Al-Sakran et al., 2018 )[1021,992] | 2226/13 (2001–2013; Marrie case definition) 1903/13 (2001–2013; CCDSS case definition) | 171.2 146.4 | 3.3% |
Saskatoon ( Hader and Yee, 2007 )[196,81018] | 254/15 (1990–2004) | 16.9 | 0.6% | |
British Columbia ( Kingwell et al., 2015 )[4058,833] | 3284/10 (1999–2008) | 328.4 | 13.2% | |
Nova Scotia ( Marrie et al., 2013 )[941,199] | 1441/16 (1995–2010) | 90.1 | 3.1% | |
Ontario ( Rotstein et al., 2018 )[11,685,304] | Standardised incidence only reported (1999–2013) | |||
Ontario ( Widdifield et al., 2015 )[11,685,304] | 15,677/10 (2001–2010) | 1567.7 | 38.0% | |
Newfoundland and Labrador ( Sloka et al., 2005 )[537,221] | 571/44 (1958–2001) | 13.0 | 1.7% | |
Alberta ( Warren et al., 2008 )[3009,249] | 9307/15 (1990–2004) | 620.5 | 9.8% | |
French West Indies (1) Total Caribbean population 2000=38,404,000 Martinique and Guadeloupe population 2000=812,000 Approximate proportion of total (unique) country population covered by regional studies in the Caribbean=2% | Martinique and Guadeloupe ( Cabre, 2009 )Martinique [387,000] Guadeloupe [425,000] | 92/15 (Martinique) 38/15 (Guadeloupe) (July 1992-June 2007) | 6.1 2.5 | 2.1% (Martinique & Guadeloupe) |
Republic of Panama (1) Total population 2000=3030,000 Republic of Panama=100% covered | Republic of Panama ( Gracia et al., 2009 ) | 144/16 (1990–2005) | 9.0 | 100% |
Europe Region | ||||
Denmark (2) Total Denmark population 2000=5341,000 Total Denmark population 2010=5547,68329 Faroe Islands Population 2000=47,000 Denmark=100% covered | Faroe Islands, Denmark ( Joensen, 2011 ) | 28/15 (1993–2007) | 1.9 | 0.9% |
Denmark ( Koch-Henriksen et al., 2018 ) | 9434/20 (1990–2009) | 471.7 | 100% | |
Finland (2) Total Finland population 2000=5188,000 Central Finland population 2000=1981,855 Vaasa=154,373 Seinäjoki=170,600 Uusimaa=1391,199 Approximate proportion of total (unique) country population covered by regional studies in Finland=45% | Northern Ostrobothnia, Northern Finland ( Krokki et al., 2011 )[372,639] | 374/16 (1992–2007) | 23.4 | 7.2% |
Central Finland ( Sarasoja et al., 2004 ) (also included Vaasa, Seinäjoki, and Uusimaa)[1981,855] | 146/10 (1989–1998) | 14.6 | 38.2% | |
Iceland (1) Total Iceland population 2000=280,000 Iceland=100% covered | Iceland ( Benedikz et al., 2002 ) | 372/50 (1950–1999) | 7.4 | 100% |
Norway (10) Total Norway population 1 Jan 2001=4503,436 Approximate proportion of total (unique) country population covered by regional studies in Norway=56% | Nordland County ( Benjaminsen et al., 2014 )[238,295] | 416/25 (1985–2009) | 16.6 | 5.3% |
Oslo ( Celius and Vandvik, 2001 )[508,726] | 374/10 (1987–1996) | 37.4 | 11.3% | |
Nord-Trøndelag County ( Dahl et al., 2004 )[127,261] | 64/10 (1989–1998) | 6.4 | 2.8% | |
Telemark County ( Flemmen et al., 2020 )
Prevalence of multiple sclerosis in rural and urban districts in Telemark county, Norway. Mult. Scler. Relat. Disord. 2020; 45102352https://doi.org/10.1016/j.msard.2020.102352 [165,595] | 380/20 (1999–2018) | 19.0 | 3.7% | |
Hordaland County ( Grytten et al., 2016 )[438,312] | 1558/61 (1953–2013) | 25.5 | 9.7% | |
Vestfold County ( Lund et al., 2014 )[215,030] | 504/21 (1983–2003) | 24.0 | 4.8% | |
Oppland County ( Risberg et al., 2011 )[183,419] | 127/10 (1989–1998) | 12.7 | 4.1% | |
Buskerud County ( Simonsen et al., 2017 )[238,833] | Average annual crude incidence 11.8 per 100,000 (2003–2012) | 29.6 | 5.3% | |
Vest-Agder County ( Vatne et al., 2011 )[156,878] | Estimated (1996–2006) | 11.5 | 3.5% | |
Møre and Romsdal County ( Willumsen et al., 2020 )[243,810] | 785/30 (1985–2014) | 26.2 | 5.4% | |
Sweden (2) Total Sweden population 2000=8882,000 Approximate proportion of total (unique) country population covered by regional studies in Sweden=6% | Värmland County ( Bostrom et al., 2009 )[275,003] | 181/10 (1991–2000) | 18.1 | 3.1% |
Västerbotten County ( Svenningsson et al., 2015 )[255,640] | 201/13 (1998–2010) | 15.5 | 2.9% | |
Croatia (1) Total Croatia population 2000=4428,000 Approximate proportion of total (unique) country population covered by regional studies in Croatia=3% | Bjelovar-Bilogora County, Croatia ( Vrabec-Matkovic et al., 2006 )[133,084 in 2001] | 47/15 (1987–2001) | 3.1 | 3.0% |
Bosnia-Herzegovina (1) Total Bosnia-Herzegovina population 2000=3767,000 | Western Herzegovina ( Klupka-Sarić et al., 2007 )[300,746 in 200348] | Average annual crude incidence 1.6 per 100,000 (1994–2003) | 4.7 | 8.0% |
France (1) Total France population 2000=59,608,000 Approximate proportion of total (unique) country population covered by regional studies in France=4% | Lorraine, France ( Debouverie et al., 2007 )[2310,376 in 199949] | 1375/10 (1993–2002) | 137.5 | 3.9% |
Germany (1) Total Germany population 2000= 81,488,000 Approximate proportion of total (unique) country population covered by regional studies in Germany=15% | Bavaria, Germany ( Daltrozzo et al., 2018 )[12,329,714 in 2001] | 18,105/10 (2006–2015) | 1810.5 | 15.1% |
Greece (3) Total Greece population 2000=11,142,000 Approximate proportion of total country population covered by regional studies in Greece=13% | Crete, Greece ( Kotzamani et al., 2012 )[579,672 in 2001] | Incidence as reported in Table 1 (1985–2008) | 23.1 | 5.2% |
Western Greece, Greece, Prefectures of Aitolokarnania, Achaia and Ilia ( Papathanasopoulos et al., 2008 )[740,506 in 200152] | 800/20 (1987–2006) | 40.0 | 6.6% | |
Province of Evros, North-Eastern Greece ( Piperidou et al., 2003 )[144,402 in 2001] | 35/11 (1989–1999) | 3.2 | 1.3% | |
Italy (13) Total Italy population 21/10/2001 census=56,995,744 Total Italy population in 2007=58,438,310 Total Italy population in 2011=59,433,744 Approximate proportion of total country population covered by regional studies in Italy=7% | South-Western part of Sardinia ( Cocco et al., 2011 )[138,765 in 200754] | Crude mean annual incidence 9.7 per 100,000 (1988–2007) | 13.5 | 0.2% |
Province of Nuoro ( Granieri et al., 2000 )[221,062] | 195/11 (1985–1995) | 17.7 | 0.4% | |
Province of Ferrara ( Granieri et al., 2007 )[344,323] | 135/10 (1990–1999) | 13.5 | 0.6% | |
Province of Padua (Padova) ( Grassivaro et al., 2019 )[849,857] | Crude incidence as reported in Table 1 (1990–2015) | 28.1 | 1.5% | |
City of Catania ( Nicoletti et al., 2011 )[313,11057] | 306/20 (1985–2004) | 15.3 | 0.5% | |
Mount Etna Regions, Catania ( Nicoletti et al., 2013 )[52,561 Western flank average population 1980–200959] [43,797 Eastern flank average population 1980–200959] | 46/20 (1990–2009; Western Flank) 53/20 (Eastern Flank) (1990–2009) | 2.3 2.7 | 0.09% Western flank 0.07% Eastern flank | |
Province of Catania ( Nicoletti et al., 2020 )
Incidence of multiple sclerosis in the province of Catania. A geo-epidemiological study. Environ. Res. 2020; 182109022https://doi.org/10.1016/j.envres.2019.109022 [1054,778] | 973/11 (2005–2015) | 88.5 | 1.9% | |
City of Biancavilla ( Patti et al., 2019 )[22,480] | 71/27 (1992–2018) | 2.6 | 0.04% | |
Province of Sassari ( Pugliatti et al., 2001 )[460,660] | 298/10 (1988–1997) | 29.8 | 0.8% | |
Province of Sassari ( Pugliatti et al., 2005 )[460,660] | 430/15 (1985–1999) | 28.7 | 0.8% | |
Province of Padova (Padua) ( Ranzato et al., 2003 )[849,857] | 580/20 (1980–1999) | 29.0 | 1.5% | |
Bagheria City ( Salemi et al., 2000 )[50,850] | 20/10 (1985–1994) | 2.0 | 0.09% | |
Province of Genoa ( Solaro et al., 2015 )[878,082] | 575/10 (1998–2007) | 57.5 | 1.5% | |
Republic of San Marino (1) Total Republic of San Marino population 2000=27,000 Republic of San Marino=100% covered | Republic of San Marino ( Granieri et al., 2008 ) | 33/16 (1990–2005) | 2.1 | 100% |
Lithuania (1) Total Lithuania population 2000=3502,000 Lithuania=100% covered | Lithuania ( Valadkeviciene et al., 2019 ) | 162+343/2 (2001 and 2015) | 252.5 | 100% |
Netherlands (1) Total Netherlands population 2000=15,926,000 Netherlands=100% covered | Netherlands ( Kramer et al., 2012 ) | 84/13 (1996–2008) | 6.5 | 100% |
Spain (2) Total Spain population 2000=40,904,000 Approximate proportion of total country population covered by regional studies in Spain=<1% | Northern Seville District of Andalucia, Southern Spain ( Izquierdo et al., 2015 )[163,324 in 2001 ( Izquierdo et al., 2015 )] | 156/20 (1991–2010) | 7.8 | 0.4% |
Bajo Aragon, Teruel, Central-Eastern Spain ( Modrego and Pina, 2003 )[58,666 in 2001 ( Modrego and Pina, 2003 )] | 42/19 (1984–2002) | 2.2 | 0.1% | |
United Kingdom (2) Total United Kingdom population 2000=58,951,000 | Cardiff, South East Wales, United Kingdom ( Modrego and Pina, 2003 )[424,633 in 2001 ( Hirst et al., 2009 )] | 582/23 (1985–2007) | 25.3 | 0.7% |
United Kingdom=100% covered | United Kingdom ( Mackenzie et al., 2014 ) | 1538/14 (1997–2010) | 109.9 | 100% |
Eastern Mediterranean Region | ||||
Iran (4) Total Iran population 2011=75,149,669 Approximate proportion of total country population covered by regional studies in Iran=26% | Mazandaran Province, Northern Iran ( Cheraghmakani et al., 2020 )
Age and sex-adjusted incidence and yearly prevalence of multiple sclerosis (MS) in Mazandaran province, Iran: an 11-years study. PLoS One. 2020; 15e0235562https://doi.org/10.1371/journal.pone.0235562 [3073,943] | 1791/10 (2009–2018) | 179.1 | 4.1% |
Tehran, Northern Iran ( Elhami et al., 2011 )[12,183,391] | 7501/20 (1989–2008) | 375.1 | 16.2% | |
Fars Province, Southern Iran ( Izadi et al., 2015 )[4596,658] | Crude incidence as in Table 1 (2003–2012) | 251.8 | 6.1% | |
Tehran, Iran ( Mohebi et al., 2019 )[12,183,391] | Crude incidence as in Table 1 (1996–2013) | 621.2 | 16.2% | |
Western Pacific Region | ||||
Australia (1) Total Australia population 2000=19,066,000 Approximate proportion of total country population covered by regional studies in Australia=<1% | Newcastle, Australia ( Ribbons et al., 2017 )[136,413 in 2001] | 132/22 (1986–2011) | 6.0 | 0.7% |
Japan (1) Total Japan population 2000=127,534,000 Approximate proportion of total country population covered by regional studies in Japan=<1% | Tokachi Province, Hokkaido, Northern Japan ( Houzen et al., 2018 )[360,992 average population 2000–2004 ( Boesen et al., 2018 )] | 62/30 (1985–2014) | 2.1 | 0.3% |
Taiwan (1) Total Taiwan population 2000=21,840,000 Taiwan=100% covered | Taiwan ( Fang et al., 2020 )
Epidemiology and comorbidities of adult multiple sclerosis and neuromyelitis optica in Taiwan, 2001-2015. Mult. Scler. Relat. Disord. 2020; 45102425https://doi.org/10.1016/j.msard.2020.102425 | 3844/10 (2006–2015) | 384.4 | 100% |
Paediatric-only studies | ||||
Canada (1) Total Canada population 2001=31,081,887 | Ontario ( Marrie et al., 2018 )[2900,00018] | 554/12 (2003–2014; Marrie case definition) 360/12 (2003–2014; CCDSS case definition) | 46.2 30.0 | 9.4% (population aged ≤18 years) |
Denmark (1) Total Denmark population 2010=5547,683 ( Boesen et al., 2018 ) | Denmark ( Boesen et al., 2018 )(paediatric-only population) [1818,787 ( Sencer, 1988 )] | 364/39 (1977–2015) 84/8 (2008–2015) | 9.3 10.5 | 32.8% (population aged <18 years) |
Kuwait (1) Total Kuwait population 2000=2051,000 Kuwait=19.9% covered | Kuwait ( Alroughani et al., 2015 )(paediatric-only population) (407,380 ( Alroughani et al., 2015 )) /2051,000) | 119/20 (1994–2013) | 6.0 | 19.9% (population aged <18 years) |
- Fang C.W.
- Wang H.P.
- Chen H.M.
- Lin J.W.
- Lin WS.
- Fang C.W.
- Wang H.P.
- Chen H.M.
- Lin J.W.
- Lin WS.
3.1.1 Italy
- Nicoletti A.
- Rascuna C.
- Boumediene F.
- Vasta R.
- Cicero C.E.
- Lo Fermo S.
- et al.
- Nicoletti A.
- Rascuna C.
- Boumediene F.
- Vasta R.
- Cicero C.E.
- Lo Fermo S.
- et al.
- Nicoletti A.
- Rascuna C.
- Boumediene F.
- Vasta R.
- Cicero C.E.
- Lo Fermo S.
- et al.

3.1.2 Canada

3.1.3 Norway
- Flemmen H.O.
- Simonsen C.S.
- Berg-Hansen P.
- Moen S.M.
- Kersten H.
- Heldal K.
- et al.

3.1.4 Denmark, Iceland, Finland and Sweden
3.1.5 Latin America and the Caribbean
3.1.6 Germany, Croatia, Bosnia-Herzegovina, France, Greece, Lithuania, the Netherlands, Spain and the United Kingdom
3.1.7 Eastern Mediterranean region
- Cheraghmakani H.
- Baghbanian S.M.
- HabibiSaravi R.
- Azar A.
- Ghasemihamedani F.
- Cheraghmakani H.
- Baghbanian S.M.
- HabibiSaravi R.
- Azar A.
- Ghasemihamedani F.