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Page 1: Disclosure · 2018. 10. 9. · Disclosure Edgardo Cristiano Department of Neurology Italian Hospital of Buenos Aires Buenos Aires, Argentina Declared declared receipt of grants and
Page 2: Disclosure · 2018. 10. 9. · Disclosure Edgardo Cristiano Department of Neurology Italian Hospital of Buenos Aires Buenos Aires, Argentina Declared declared receipt of grants and

Disclosure

Edgardo CristianoDepartment of NeurologyItalian Hospital of Buenos AiresBuenos Aires, Argentina

Declared declared receipt of grants and contract from: Merck, Novartis and of honoraria and consultation fees from: Biogen, Merck, Novartis. He declared also participation in a company sponsored speaker’s bureau: Biogen, Merck, Novartis, Genzyme, Roche.

Page 3: Disclosure · 2018. 10. 9. · Disclosure Edgardo Cristiano Department of Neurology Italian Hospital of Buenos Aires Buenos Aires, Argentina Declared declared receipt of grants and

Multiple Sclerosis in Latin America: epidemiology and clinical severity

E. Cristiano

Argentina

Page 4: Disclosure · 2018. 10. 9. · Disclosure Edgardo Cristiano Department of Neurology Italian Hospital of Buenos Aires Buenos Aires, Argentina Declared declared receipt of grants and

AmerindiansAsiaticAfricansMestizosMulatosCaucasianZambosTri-racial(Africans – Amerindian– European)

Latitude 32º north

Multiple Sclerosis in Caucasian and Latino Americans. Autoimmunity 2011: 44: 571-575

Latin America

Surface: 21.069.500 Km2

Population: 580.000.000 inhab

Latitude 56º south

Languages: spanish and portuguese

Page 5: Disclosure · 2018. 10. 9. · Disclosure Edgardo Cristiano Department of Neurology Italian Hospital of Buenos Aires Buenos Aires, Argentina Declared declared receipt of grants and

Prevalence, incidence and genetics

Page 6: Disclosure · 2018. 10. 9. · Disclosure Edgardo Cristiano Department of Neurology Italian Hospital of Buenos Aires Buenos Aires, Argentina Declared declared receipt of grants and

Kurtzke JF. The geographical distribution of multiple sclerosis – An update with special reference to

Europe and the Mediterranean region Acta Neurol Scand 1980; 62: 65-80

1980

Page 7: Disclosure · 2018. 10. 9. · Disclosure Edgardo Cristiano Department of Neurology Italian Hospital of Buenos Aires Buenos Aires, Argentina Declared declared receipt of grants and

MS Atlas 2013 (https://www.msif.org/wp-content/uploads/2014/09/Atlas-of-MS.pdf )

Page 8: Disclosure · 2018. 10. 9. · Disclosure Edgardo Cristiano Department of Neurology Italian Hospital of Buenos Aires Buenos Aires, Argentina Declared declared receipt of grants and

Cristiano E et al. Multiple Sclerosis Journal 2012; 0: 1-11

Page 9: Disclosure · 2018. 10. 9. · Disclosure Edgardo Cristiano Department of Neurology Italian Hospital of Buenos Aires Buenos Aires, Argentina Declared declared receipt of grants and

Cristiano E et al. Multiple Sclerosis Journal 2012; 0: 1-11

Prevalence studies

Lower prevalence in Ecuador, Colombia and Panamá(0.75 a 6.5/100.000 inhab.)

Higher prevalence in Brazil and Argentina(12-21.5/100.000 inhab.)

High dispersion in the other areas

Page 10: Disclosure · 2018. 10. 9. · Disclosure Edgardo Cristiano Department of Neurology Italian Hospital of Buenos Aires Buenos Aires, Argentina Declared declared receipt of grants and

Cristiano E et al. Multiple Sclerosis Journal 2012; 0: 1-11

Incidence studies

Phenotypes

Only 3 countries evaluated incidence: French West Indies, Panama and Argentina

(0.60 a 1.76/100.000 person/year)

The most prevalent phenotype was relapsing-remitting

Page 11: Disclosure · 2018. 10. 9. · Disclosure Edgardo Cristiano Department of Neurology Italian Hospital of Buenos Aires Buenos Aires, Argentina Declared declared receipt of grants and

• Argentina (12 – 20 - 38 / 100.000 )

• Brasil (4.3 – 15 – 18.1 / 100.000)

• Colombia (1.48 – 4.98 / 100.000)

• México (1.6 – 6.3 – 13.0 / 100.000)

Prevalence increases in successive studies

Page 12: Disclosure · 2018. 10. 9. · Disclosure Edgardo Cristiano Department of Neurology Italian Hospital of Buenos Aires Buenos Aires, Argentina Declared declared receipt of grants and

Estimated prevalence:

13.5-19.8/100.000 inh.

Cristiano et al. Eur J Neurol 2009; 16: 183-187

• Área geográfica:• C.A.B.A. y gran Buenos Aires

• Superficie: 4758 km2

• Población: 12.594.974 habitantes (Censo 1990)

• Clima subtropical

• Fuentes de información:• EMA (Asociación de pacientes)

• Hospital Italiano de Buenos Aires

• Hospital Británico

• Hospital Ramos Mejía

Page 13: Disclosure · 2018. 10. 9. · Disclosure Edgardo Cristiano Department of Neurology Italian Hospital of Buenos Aires Buenos Aires, Argentina Declared declared receipt of grants and

• Área geográfica:• C.A.B.A. y gran Buenos Aires

• Superficie: 4758 km2

• Población: 12.806.866 habitantes (Censo 2010)

• Clima subtropical

• Fuentes de información:• ALCEM (Asociación de pacientes)

• Hospital Italiano de Buenos Aires

• Hospital Británico

• Hospital Ramos Mejía

• FLENI

• INEBA

Estimated total size Confidence Interval % Prevalence rate (per 100.000) 95%CI

4901 4623 - 5276 38.2 36.1 – 41.2

Estimated prevalence: 38.2/100.000 inh.

Multiple Sclerosis and Related Disorders 9 (2016) 91–94

Page 14: Disclosure · 2018. 10. 9. · Disclosure Edgardo Cristiano Department of Neurology Italian Hospital of Buenos Aires Buenos Aires, Argentina Declared declared receipt of grants and

Incidence density: 1.76 cases/year/100,000 persons

Eur J Neurol 2010; 17: 479-482

Page 15: Disclosure · 2018. 10. 9. · Disclosure Edgardo Cristiano Department of Neurology Italian Hospital of Buenos Aires Buenos Aires, Argentina Declared declared receipt of grants and

Se observó un incremento en la densidad de incidencia

(3/100.000/año) respecto del estudio previo

Cristiano et al. Neurol SCI 2016; 37: 1621-1626

Page 16: Disclosure · 2018. 10. 9. · Disclosure Edgardo Cristiano Department of Neurology Italian Hospital of Buenos Aires Buenos Aires, Argentina Declared declared receipt of grants and

Results: 165,456 subjects were followed for a total of 1,488,575 person-years, of whom 42 developed MS. Incidence density was 3/100,000 person-years (95% CI: 2.1 – 3.5/100,000 person-years). During this period (1992-2013), the incidence rate in women increased from 1/100,000 (95%CI 0.8-1.6) to 4.9/100,000 (95%CI 4.1-5.4) (p<0.001), while in men the incidence ranged from 1.4/100,000 (95%CI 1-1.7) to 1.8 (1.3-2.1) (p=0.16)

1,4

4,9

1,8

3,0

, Neurol Sci, June 2016

Page 17: Disclosure · 2018. 10. 9. · Disclosure Edgardo Cristiano Department of Neurology Italian Hospital of Buenos Aires Buenos Aires, Argentina Declared declared receipt of grants and
Page 18: Disclosure · 2018. 10. 9. · Disclosure Edgardo Cristiano Department of Neurology Italian Hospital of Buenos Aires Buenos Aires, Argentina Declared declared receipt of grants and

Multiple Sclerosis 2008; 14: 656-662

• Ubicada en el extremo sur del continente americano• Latitud: -39° y -55°S• Superficie: 1.768.165 km2• Abarca las provincias más australes de:

• Neuquén• Río Negro• Chubut• Santa Cruz• Tierra del Fuego

• Población: 40.117.096 habitantes (INDEC – Censo 2010)

• Clima desértico y semidesértico

Page 19: Disclosure · 2018. 10. 9. · Disclosure Edgardo Cristiano Department of Neurology Italian Hospital of Buenos Aires Buenos Aires, Argentina Declared declared receipt of grants and

11 a 69/100.000NO differences between -20º y -55º

18/100.000

1318

Page 20: Disclosure · 2018. 10. 9. · Disclosure Edgardo Cristiano Department of Neurology Italian Hospital of Buenos Aires Buenos Aires, Argentina Declared declared receipt of grants and

MS disease course in Latinamerica

Page 21: Disclosure · 2018. 10. 9. · Disclosure Edgardo Cristiano Department of Neurology Italian Hospital of Buenos Aires Buenos Aires, Argentina Declared declared receipt of grants and

RRMS was the more prevalent subtype (48 – 91%)

Multiple Sclerosis – Published on line 8 october 2012

Page 22: Disclosure · 2018. 10. 9. · Disclosure Edgardo Cristiano Department of Neurology Italian Hospital of Buenos Aires Buenos Aires, Argentina Declared declared receipt of grants and

Rojas et al. MSJ Experimental Translational Clinical 2015; 1: 1-6

Page 23: Disclosure · 2018. 10. 9. · Disclosure Edgardo Cristiano Department of Neurology Italian Hospital of Buenos Aires Buenos Aires, Argentina Declared declared receipt of grants and

Rojas et al. MSJ Experimental Translational Clinical 2015; 1: 1-6

No differencies found between regions nor hemisphers regarding disease severity (MSSS)

Page 24: Disclosure · 2018. 10. 9. · Disclosure Edgardo Cristiano Department of Neurology Italian Hospital of Buenos Aires Buenos Aires, Argentina Declared declared receipt of grants and

Rojas et al. Multiple Sclerosis and Related Disorders 2016; 6: 54-56

Se observó una anticipación en la

edad de inicio en las generaciones

más jóvenes de las formas familiares

Page 25: Disclosure · 2018. 10. 9. · Disclosure Edgardo Cristiano Department of Neurology Italian Hospital of Buenos Aires Buenos Aires, Argentina Declared declared receipt of grants and

Genes and environment

Page 26: Disclosure · 2018. 10. 9. · Disclosure Edgardo Cristiano Department of Neurology Italian Hospital of Buenos Aires Buenos Aires, Argentina Declared declared receipt of grants and

Studies in native populations

Lacandones - México

Page 27: Disclosure · 2018. 10. 9. · Disclosure Edgardo Cristiano Department of Neurology Italian Hospital of Buenos Aires Buenos Aires, Argentina Declared declared receipt of grants and

• Clinical and epidemiological data were obtained from 5,372 Lacandonias• 350 DNA samples were obtained

• NO persons with MS or NMO symptoms were identified

Page 28: Disclosure · 2018. 10. 9. · Disclosure Edgardo Cristiano Department of Neurology Italian Hospital of Buenos Aires Buenos Aires, Argentina Declared declared receipt of grants and
Page 29: Disclosure · 2018. 10. 9. · Disclosure Edgardo Cristiano Department of Neurology Italian Hospital of Buenos Aires Buenos Aires, Argentina Declared declared receipt of grants and

Activación de la función

supresora de las Treg

(IL10 - TGF)

Apoptosis

Inhibición de la

activación

Ann Neurol 2007; 61: 97-108

Page 30: Disclosure · 2018. 10. 9. · Disclosure Edgardo Cristiano Department of Neurology Italian Hospital of Buenos Aires Buenos Aires, Argentina Declared declared receipt of grants and

Ann Neurol 2007; 61: 97-108

Page 31: Disclosure · 2018. 10. 9. · Disclosure Edgardo Cristiano Department of Neurology Italian Hospital of Buenos Aires Buenos Aires, Argentina Declared declared receipt of grants and

Low-medium prevalence in LATAM

• Probable reasons:

– Genetic background

• Very heterogeneous population

• Protective genes (?)

– Environmental factors

• Solar exposure

• Vitamin D levels

• Diet

• Hygiene hypothesis

– Subdiagnosis

Page 32: Disclosure · 2018. 10. 9. · Disclosure Edgardo Cristiano Department of Neurology Italian Hospital of Buenos Aires Buenos Aires, Argentina Declared declared receipt of grants and

• Large emerging data from Latam in the last 20 years

• Low-medium risk for MS in LATAM (range 1,5-30)

• Prevelence and incidence increase with new studies

• Similar phenotypes

• Similar severity

Conclusions

Page 33: Disclosure · 2018. 10. 9. · Disclosure Edgardo Cristiano Department of Neurology Italian Hospital of Buenos Aires Buenos Aires, Argentina Declared declared receipt of grants and

www.esclerosismultiple.org