title: Central Nervous System Idiopathic Inflammatory Demyelinating Disorders in South Americans: A Descriptive, Multicenter, Cross-Sectional Study.
abstract: The idiopathic inflammatory demyelinating disease (IIDD) spectrum has been investigated among different populations, and the results have indicated a low relative frequency of neuromyelitis optica (NMO) among multiple sclerosis (MS) cases in whites (1.2%-1.5%), increasing in Mestizos (8%) and Africans (15.4%-27.5%) living in areas of low MS prevalence. South America (SA) was colonized by Europeans from the Iberian Peninsula, and their miscegenation with natives and Africans slaves resulted in significant racial mixing. The current study analyzed the IIDD spectrum in SA after accounting for the ethnic heterogeneity of its population. A cross-sectional multicenter study was performed. Only individuals followed in 2011 with a confirmed diagnosis of IIDD using new diagnostic criteria were considered eligible. Patients' demographic, clinical and laboratory data were collected. In all, 1,917 individuals from 22 MS centers were included (73.7% female, 63.0% white, 28.0% African, 7.0% Mestizo, and 0.2% Asian). The main disease categories and their associated frequencies were MS (76.9%), NMO (11.8%), other NMO syndromes (6.5%), CIS (3.5%), ADEM (1.0%), and acute encephalopathy (0.4%). Females predominated in all main categories. The white ethnicity also predominated, except in NMO. Except in ADEM, the disease onset occurred between 20 and 39 years old, early onset in 8.2% of all cases, and late onset occurred in 8.9%. The long-term morbidity after a mean disease time of 9.28±7.7 years was characterized by mild disability in all categories except in NMO, which was scored as moderate. Disease time among those with MS was positively correlated with the expanded disability status scale (EDSS) score (r=0.374; p=<0.001). This correlation was not observed in people with NMO or those with other NMO spectrum disorders (NMOSDs). Among patients with NMO, 83.2% showed a relapsing-remitting course, and 16.8% showed a monophasic course. The NMO-IgG antibody tested using indirect immunofluorescence (IIF) with a composite substrate of mouse tissues in 200 NMOSD cases was positive in people with NMO (95/162; 58.6%), longitudinally extensive transverse myelitis (10/30; 33.3%) and bilateral or recurrent optic neuritis (8/8; 100%). No association of NMO-IgG antibody positivity was found with gender, age at onset, ethnicity, early or late onset forms, disease course, or long-term severe disability. The relative frequency of NMO among relapsing-remitting MS (RRMS) + NMO cases in SA was 14.0%. Despite the high degree of miscegenation found in SA, MS affects three quarters of all patients with IIDD, mainly white young women who share similar clinical characteristics to those in Western populations in the northern hemisphere, with the exception of ethnicity; approximately one-third of all cases occur among non-white individuals. At the last assessment, the majority of RRMS patients showed mild disability, and the risk for secondary progression was significantly superior among those of African ethnicity. NMO comprises 11.8% of all IIDD cases in SA, affecting mostly young African-Brazilian women, evolving with a recurrent course and causing moderate or severe disability in both ethnic groups. The South-North gradient with increasing NMO and non-white individuals from Argentina, Paraguay, Brazil and Venezuela confirmed previous studies showing a higher frequency of NMO among non-white populations.
authors.affiliation: Department of Neurology, Universidade Federal do Estado do Rio de Janeiro, Rio de Janeiro, Brazil; Department of Neurology, Hospital Federal da Lagoa, Ministério da Saúde, Rio de Janeiro, Brazil; Clinica de Neuroimunologia, Rio de Janeiro, Brazil.
authors.forename: Regina Maria
authors.initials: RM
authors.lastname: Papais-Alvarenga
authors.affiliation: Department of Neurology, Universidade Federal do Estado do Rio de Janeiro, Rio de Janeiro, Brazil; Department of Neurology, Hospital Federal da Lagoa, Ministério da Saúde, Rio de Janeiro, Brazil; Clinica de Neuroimunologia, Rio de Janeiro, Brazil.
authors.forename: Claudia Cristina Ferreira
authors.initials: CC
authors.lastname: Vasconcelos
authors.affiliation: Department of Neurology, Hospital Británico, Buenos Aires, Argentina.
authors.forename: Adriana
authors.initials: A
authors.lastname: Carra
authors.affiliation: Department of Neurology, Hospital Clínico de Maracaibo, Maracaibo, Venezuela.
authors.forename: Ibis Soto
authors.initials: IS
authors.lastname: de Castillo
authors.affiliation: Department of Neurology, Instituto de Prevision Social, Asunción, Paraguay.
authors.forename: Sara
authors.initials: S
authors.lastname: Florentin
authors.affiliation: Department of Neurology, Universidad Unida, Asunción, Paraguay.
authors.forename: Fernando Hamuy
authors.initials: FH
authors.lastname: Diaz de Bedoya
authors.affiliation: Department of Neurology, John Hopkins, Washington, District of Columbia, United States of America.
authors.forename: Raul
authors.initials: R
authors.lastname: Mandler
authors.affiliation: Department of Neurology, Universidade Federal do Estado do Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Luiza Campanella
authors.initials: LC
authors.lastname: de Siervi
authors.affiliation: Department of Neurology, Santa Casa da Misericórdia, Rio de Janeiro, Brazil.
authors.forename: Maria Lúcia Vellutini
authors.initials: ML
authors.lastname: Pimentel
authors.affiliation: Department of Neurology, Universidade Federal do Estado do Rio de Janeiro, Rio de Janeiro, Brazil; Department of Neurology, Hospital Federal da Lagoa, Ministério da Saúde, Rio de Janeiro, Brazil; Department of Neurology, Rede Sarah de Reabilitação, Rio de Janeiro, Brazil.
authors.forename: Marina Papais
authors.initials: MP
authors.lastname: Alvarenga
authors.affiliation: Department of Neurology, Universidade Federal do Estado do Rio de Janeiro, Rio de Janeiro, Brazil; Department of Neurology, Hospital Federal da Lagoa, Ministério da Saúde, Rio de Janeiro, Brazil; Clinica de Neuroimunologia, Rio de Janeiro, Brazil.
authors.forename: Marcos Papais
authors.initials: MP
authors.lastname: Alvarenga
authors.affiliation: Department of Neurology, Centro de Reabilitação Integral Dom Aquino Corrêa, Mato Grosso, Brazil.
authors.forename: Anderson Kuntz
authors.initials: AK
authors.lastname: Grzesiuk
authors.affiliation: Department of Neurology, Universidade Severino Sombra, Vassouras, Rio de Janeiro, Brazil.
authors.forename: Ana Beatriz Calmon
authors.initials: AB
authors.lastname: Gama Pereira
authors.affiliation: Department of Neurology, Santa Casa da Misericórdia, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Antonio Pereira
authors.initials: AP
authors.lastname: Gomes Neto
authors.affiliation: Department of Neurology, Instituto de Prevision Social, Asunción, Paraguay.
authors.forename: Carolina
authors.initials: C
authors.lastname: Velasquez
authors.affiliation: Department of Neurology, Hospital Universitário, Caracas, Venezuela.
authors.forename: Carlos
authors.initials: C
authors.lastname: Soublette
authors.affiliation: Department of Neurology, Instituto de Prevision Social, Asunción, Paraguay.
authors.forename: Cynthia Veronica
authors.initials: CV
authors.lastname: Fleitas
authors.affiliation: Department of Neurology, Hospital das Clínicas da Universidade Federal de Goiás, Goiania, Brazil.
authors.forename: Denise Sisteroli
authors.initials: DS
authors.lastname: Diniz
authors.affiliation: Department of Neurology, Hospital Universitário, Caracas, Venezuela.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Armas
authors.affiliation: Department of Neurology, Universidade Federal do Estado do Rio de Janeiro, Rio de Janeiro, Brazil; Department of Neurology, Hospital Federal da Lagoa, Ministério da Saúde, Rio de Janeiro, Brazil.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Batista
authors.affiliation: Department of Neurology, Hospital Clínico de Maracaibo, Maracaibo, Venezuela.
authors.forename: Freda
authors.initials: F
authors.lastname: Hernandez
authors.affiliation: Department of Neurology, Universidade Federal do Estado do Rio de Janeiro, Rio de Janeiro, Brazil; Neuroclinica, Volta Redonda, Rio de Janeiro, Brazil.
authors.forename: Fernanda Ferreira Chaves da Costa
authors.initials: FF
authors.lastname: Pereira
authors.affiliation: Department of Neurology, Universidade Federal do Estado do Rio de Janeiro, Rio de Janeiro, Brazil; Department of Neurology, Universidade Federal de Mato Grosso, Cuiabá, Brazil.
authors.forename: Heloise Helena
authors.initials: HH
authors.lastname: Siqueira
authors.affiliation: Department of Neurology, Hospital Ofir Loiola, Pará, Brazil.
authors.forename: Hideraldo
authors.initials: H
authors.lastname: Cabeça
authors.affiliation: Department of Neurology, Instituto de Prevision Social, Asunción, Paraguay.
authors.forename: Jose
authors.initials: J
authors.lastname: Sanchez
authors.affiliation: Department of Neurology, Centro de Referência em Esclerose Múltipla do Litoral Paulista, São Paulo, Brazil.
authors.forename: Joseph Bruno Bidin
authors.initials: JB
authors.lastname: Brooks
authors.affiliation: Department of Neurology, Joinville, Santa Catarina, Brazil.
authors.forename: Marcus Vinicius
authors.initials: MV
authors.lastname: Gonçalves
authors.affiliation: Department of Neurology, Universidade Federal do Estado do Rio de Janeiro, Rio de Janeiro, Brazil; Department of Neurology, Rede Sarah de Reabilitação, Rio de Janeiro, Brazil.
authors.forename: Maria Cristina Del Negro
authors.initials: MC
authors.lastname: Barroso
authors.affiliation: Department of Neurology, Hospital JM de los Rios, Caracas, Venezuela.
authors.forename: Maria Elena
authors.initials: ME
authors.lastname: Ravelo
authors.affiliation: Department of Neurology, Hospital Clínico de Maracaibo, Maracaibo, Venezuela.
authors.forename: Maria Carlota
authors.initials: MC
authors.lastname: Castillo
authors.affiliation: Department of Neurology, Hospital da Restauração, Recife, Pernambuco, Brazil.
authors.forename: Maria Lúcia Brito
authors.initials: ML
authors.lastname: Ferreira
authors.affiliation: Department of Neurology, Hospital Santa Marcelina, São Paulo, Brazil.
authors.forename: Maria Sheila Guimarães
authors.initials: MS
authors.lastname: Rocha
authors.affiliation: Clínica neurológica, Paraná, Brazil.
authors.forename: Monica Koncke Fiuza
authors.initials: MK
authors.lastname: Parolin
authors.affiliation: Department of Neurology, Hospital Clínico de Maracaibo, Maracaibo, Venezuela.
authors.forename: Omaira
authors.initials: O
authors.lastname: Molina
authors.affiliation: Department of Neurology, Universidade Federal do Estado do Rio de Janeiro, Rio de Janeiro, Brazil; Department of Neurology, Rede Sarah de Reabilitação, Rio de Janeiro, Brazil.
authors.forename: Patricia Beatriz Christino
authors.initials: PB
authors.lastname: Marinho
authors.affiliation: Department of Neurology, Santa Casa da Misericórdia, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Paulo Pereira
authors.initials: PP
authors.lastname: Christo
authors.affiliation: Department of Neurology, Santa Casa da Misericórdia, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Renata
authors.initials: R
authors.lastname: Brant de Souza
authors.affiliation: Department of Neurology, Universidade Federal do Estado do Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Silvio
authors.initials: S
authors.lastname: Pessanha Neto
authors.affiliation: Department of Neurology, Hospital Federal da Lagoa, Ministério da Saúde, Rio de Janeiro, Brazil.
authors.forename: Solange Maria das Graças
authors.initials: SM
authors.lastname: Camargo
authors.affiliation: Department of Neurology, Imperial Hospital de Caridade, Florianópolis, Santa Catarina, Brazil.
authors.forename: Suzana Costa
authors.initials: SC
authors.lastname: Machado
authors.affiliation: Department of Neurology, Universidade Federal do Estado do Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Vanderson Carvalho
authors.initials: VC
authors.lastname: Neri
authors.affiliation: Department of Neurology, Universidade Federal do Estado do Rio de Janeiro, Rio de Janeiro, Brazil; Department of Neurology, Centro de Referência em Esclerose Múltipla do Litoral Paulista, São Paulo, Brazil.
authors.forename: Yara Dadalti
authors.initials: YD
authors.lastname: Fragoso
authors.affiliation: Department of Neurology, Universidade Federal do Estado do Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Helcio
authors.initials: H
authors.lastname: Alvarenga
authors.affiliation: Department of Neurology, Universidade Federal do Estado do Rio de Janeiro, Rio de Janeiro, Brazil; Clinical Research Division Instituto Nacional de Câncer, Rio de Janeiro, Brazil.
authors.forename: Luiz Claudio Santos
authors.initials: LC
authors.lastname: Thuler
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D000818:Animals; D002648:Child; D002675:Child, Preschool; D003430:Cross-Sectional Studies; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D051379:Mice; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000175:diagnosis / Q000208:ethnology* / Q000401:mortality* / Q000628:therapy; D009471:Neuromyelitis Optica / Q000175:diagnosis / Q000208:ethnology* / Q000401:mortality* / Q000628:therapy; D012737:Sex Factors; D013020:South America / Q000453:epidemiology / Q000208:ethnology