Multiple Sclerosis and Related Disorders (2013) 2, 80–89

Available online at www.sciencedirect.com

journal homepage: www.elsevier.com/locate/msard

REVIEW

Multiple sclerosis in Colombia and other Latin

American Countries
Jaime Toroa,b,c,d,n, Simón Ca rdenasd, Carlos Fernando Martı́neza,c,
 Urrutiab, Camilo Dı́azd
Julian

a
Department of Neurology, Hospital Universitario—Fundaci ón Santa Fe de Bogota , Calle 119 No. 7-75, Bogota , Colombia
b
School of Medicine, Universidad de Los Andes, Carrera 1 No. 18 A-12, Bogota , Colombia
c
School of Medicine, Universidad El Bosque, Carrera 7B Bis No. 132-11, Bogota , Colombia
d
Multiple Sclerosis Investigation Group, Hospital Universitario—Fundaci ón Santa Fe de Bogota , Avenida 9 No. 117-20
Oficina 409, Colombia

Received 10 August 2012; received in revised form 30 August 2012; accepted 5 September 2012

KEYWORDS Abstract
Latin America; The spectrum of multiple sclerosis (MS) in Latin America is characterized by geographic and racial/
Colombia; genetic particularities. In this review we describe major studies of MS epidemiology, genetics, and
Multiple sclerosis; clinical presentation in Latin America, with a focus on Colombia. We also consider the influence of
Health policy; national health care systems on the treatment of MS in Latin American patients. Epidemiologic
Prevalence;
studies indicate that the regional incidence of MS in Latin America is more complex than once
Review
thought, and broadly consistent with the geographical (latitudinal) distribution of MS in other parts of
the world. Low prevalence of MS is considered to be o5/100.000 inhabitants and high prevalence
430/100,000. Colombia is considered a low-risk region for MS, as are other countries located near
the equator, such as Panama and Ecuador. By contrast, Latin American countries located farther from
the equator are medium or high-risk regions. National health care systems generally cover MS
treatment, although bureaucratic problems sometimes interfere with delivery of high-cost medica-
tions and access to diagnostic tests, particularly in rural areas. The population of Colombia is racially
diverse and genetically heterogeneous, making it difficult to study genetic associations within a
complex disease such as MS. The clinical spectrum of MS in Latin America is similar to that of Europe
or North America.
& 2012 Published by Elsevier B.V.

Contents

1. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 81
2. Health care system . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 81

n

Corresponding author. Asociación Medica de Los Andes, Avenida 9 No. 117-20 Oficina 409, Bogota , Colombia. Tel.: +57 1 2150169;
fax: +57 1 2150205.
E-mail address: jtoro@uniandes.edu.co (J. Toro).

2211-0348/$ - see front matter & 2012 Published by Elsevier B.V.

http://dx.doi.org/10.1016/j.msard.2012.09.001

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Multiple sclerosis in Colombia and other Latin American Countries 81

3. Epidemiology. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 83
4. Genetics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 84
5. Clinical course . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 85
Conflict of Interest . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 87
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 87

1. Introduction Bogota (as compared to 27% previously), including the poor,

formal and informal employees, and their families. Since
The literature review presented in this paper is based on a then, health care organizations have been required to cover
search of MEDLINE and the Literatura Latino-Americana y del modern diagnostic tests and treatments for patients with
Caribe en Ciencias de la Salud (LILACS) database for all MS. These changes offer a unique opportunity to estimate
published articles on multiple sclerosis (MS) in Latin America. the prevalence of MS in Colombia more accurately than was
Among Latin American countries, Colombia is considered possible previously.
to have a particularly low prevalence of multiple sclerosis
(MS). According to Kurtzke (1975), the regional prevalence
of MS can be categorized according to disease frequency: 2. Health care system
low (o5 cases per 100,000 inhabitants), medium (5–30 cases
per 100,000 inhabitants), and high (430 cases per 100,000 The Political Constitution and Constitutional Court of Colombia
inhabitants). enshrine a fundamental right to health care, which can be
Bogota , the capital of Colombia, is located at a mean upheld judicially through a constitutional protection writ
altitude of 2640 m above sea level, has an area of 1587 km2, called tutela (Constitución Polı́tica de Colombia (1991);
and is located at geographic coordinates 4135N 74104W. The Corte Constitucional de Colombia (2008)). Thus, every Colom-
temperature of the city varies between 8 1C and 16 1C year- bian has the right to a basic health benefits package, the Plan
round, unlike the temperature of Argentina, Uruguay, Chile, Obligatorio de Salud (POS), which is provided under a national
or Brazil, which varies by season. Bogota has approximately insurance program and administered by either public or
8,000,000 inhabitants and its population increases annually private Health Promoting Entities (EPSs; the local equivalent
at a rate of 2.4%. of health maintenance organizations). Although the POS
The population of modern-day Colombia is genetically covers an array of services, including some high-cost diagnos-
diverse and includes people with Native American, European, tic and medical procedures for both acute and chronic
and African origins. There is no significant immigration to conditions, patients can request types of care not included
Bogota from European countries. It is likely that the low in the POS by means of the tutela when their health is
prevalence of MS in Colombia (Toro et al., 2007; Sanchez threatened demonstrably by a lack of such care. Furthermore
et al., 2000) and other Latin American countries as compared to in Colombia and many Latin American countries, families are
other parts of the world, is related to genetic and environ- closely involved in the long-term care of patients with MS.
mental differences between European/North American/Asian/ Health insurance expansion through the POS has resulted in
African and Latin American populations. Access to advanced increased risk protection, usage of traditionally under-utilized
imaging and medical care may also contribute to the observed preventative services, and reduced out-of-pocket expenses for
differences in disease prevalence among some Latin American health care services (Castaño et al., 2002). This system has
countries. given most MS patients access to high-cost diagnostic proce-
Before the advent of modern techniques for the study of dures, such as visual evoked potential (VEP) tests and magnetic
genetic contributions to disease, it was proposed that resonance imaging (MRI) scans, irrespective of income (CRES,
differences in sunlight exposure may contribute to the 2011). Therefore, up to 80.4% of MS patients in Colombia have
geographic (latitude-based) distribution of MS. In Tasmania received at least one MRI scan (Toro et al., 2007). Individual
a case–control study showed that higher sun exposure during patients can request excluded interventions by means of the
childhood and early adolescence is associated with a lower tutela, thus Colombian MS patients do have access to a
risk of MS (van der Mei et al., 2003). More recently, the mechanism by which they can, in principle, secure state-of-
geographic distribution has been attributed to genetic the-art care.
differences among populations, and growing evidence sug- The most effective health care policies for the management
gests that vitamin D insufficiency may account for the of MS at a population level remain to be established. Differ-
latitudinal gradient of MS (Munger et al., 2006; Beretich ences in policy among Latin American countries and in the rest
et al., 2009). The disease seems unlikely to result from a of the world highlight this lack of consensus. For example, in
single causative event; instead, MS seems to develop in Brazil, clinical guidelines establish which types of care are
genetically susceptible populations as a result of environ- covered by the national health care system (Brazilian Ministry
mental exposures like sunlight, which might influence levels of Health, 2010). In Chile, MS is included as a disease category
of vitamin D. On the other hand a lower risk of MS could covered through the national health care program, Acceso
potentially be explained by direct protective effect of Universal conGarantias Explicitas (AUGE), as of 2010 (Chilean
ultraviolet B radiation (UVB), independent of vitamin D Ministry of Health, 2010a, b). Clinical guidelines of the Chilean
synthesis (Lucas and Ponsonby, 2006). Ministry of Health offer treatment options and diagnostic
In 1993, health care reform resulted in an expansion of procedures (Chilean Ministry of Health, 2010a, b). In Uruguay,
health insurance coverage to 70% of the population of the National Resource Fund (FNR) ensures financing of

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82 J. Toro et al.

Table 1 Approach to the diagnosis and treatment of Table 1 (continued )

Multiple Sclerosis in Latin America.
Country Coverage Comments
Country Coverage Comments Patients with PPMS
Colombia MRI scans subtype are excluded
Important
VEP tests from coverage
administrative
Venezuela IFNb, GA, other In 2006 approximately
barriers to access that
medications affecting 87% of all MS patients
limit the benefits to
disease progression were receiving free
patients
CSF tests Treatment with IFNb, integral treatment
natalizumab, GA or through the
mitoxantrone is not Venezuelan Institute
covered of Social Security
Inpatient treatment Therapies for disease
with IV steroids for complications (e.g.
flares botulinum toxin for
Physical therapy spasticity)
Brazil MRI scans Argentina IFNb Bureaucratic
inefficiencies
VEP tests
frequently delay
CSF tests
access to treatment
IV
methylprednisolone CSF, cerebrospinal fluid; IFNg, interferon beta; IVIG, intra-
for flares venous immunoglobulin; GA, glatiramer acetate; GI, gastro-
IFNb or GA (first line) intestinal; MRI, magnetic resonance imagining; PPMS,
Natalizumab (second primary-progressive multiple sclerosis; RRMS, relapsing-
line) remitting multiple sclerosis; SPMS, secondary-progressive
Chile Yearly follow-up MRI Treatment offered for multiple sclerosis; VEP, visual evoked potentials.
scan patients with RRMS
and SPMS with
VEP tests relapses treatment only for patients with a reasonable life expectancy
CSF tests as a result of adequate response to therapy. To qualify for
IFNb-1 A, IFNb-1B, GA treatment, patients must provide documentation that the
(first line) center requesting coverage is capable of providing integral,
Mitoxantrone, IVIG, multidisciplinary treatment including psychosocial support and
azathioprine (second rehabilitation therapy. This documentation must be provided
line) anew each month to secure funding for the following month’s
Hospitalizations for: treatment (National Resource Fund, 2008). In Venezuela, all
diagnostic purposes, citizens have a right to health care including high-cost medica-
treatment of tions and treatments (Venezuelan Institute for Social Security,
exacerbations with IV 2009). In Argentina, the Special Programs Administration (APE)
methylprednisolone, covers treatment with IFNb only for patients with RRMS or for
treatment of disease SPMS with relapses (Special Programs Administration, 2004). By
complications law, health insurance agencies are obligated to fund this
Psychological therapy for all eligible patients (Instituto de Estudios sobre
support, treatment Polı́ticas de Salud, 2011) (see Table 1 for a summary of diagnosis
and rehabilitation for and management of MS in Latin America). Recently fingolimod
fatigue, spasticity, has been introduced in several countries of Latin America
ataxia, tremor, (Argentina, Brazil, Chile, Colombia, Guatemala, Mexico,
urinary and GI tract Panama, Peru and Venezuela).
dysfunction, pain, The most common problem in MS treatment in Colombia
emotional liability and elsewhere in Latin America is the intermittent use of
Uruguay IFNb, GA Treatment offered IFNb due to problems with bureaucracy and medication
only to patients delivery by the Health Care System. It is well-known that
meeting detailed intermittent use of this medication, as is common in
inclusion and Colombia and Latin America, is associated with no benefit
exclusion criteria in terms of relapsing of the disease (Tan et al., 2011).
regarding age, co- Another issue that one must consider in Latin America
morbidities, quality of regarding treatment of MS is the physician–industry relation-
life, and prognosis ship through educational activities, meetings and seminars
which create an unconscious social expectation of recipro-
city that could influence many of the doctors prescribing

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Multiple sclerosis in Colombia and other Latin American Countries
behavior. However, relationships between physicians and
industry can have some positive effects on patients care.
In Latin America there is an average of one neurologist
per 202,000 inhabitants (WFN, 2001). A recent survey of 855
neurologists in nine out of 20 Latin American countries
(Argentina, Brazil, Chile, Colombia, Mexico, Panama , Perú,
Uruguay and Venezuela) found that 94% reported sufficient
patient access to MRI scans, 82% reported adequate patient
access to VEP tests, and only 45% reported access to CSF
oligoclonal band detection tests, in their home countries.
Although most respondents indicated that their first-line
treatment of choice is GA or IFNb, only 64% reported that
generic versions of these drugs are approved for use in their
home countries, and all agreed that health care systems
need to improve coverage offered at a population level
(Carra et al., 2011). These experiences are by no means
confined to the developing world. In England and Wales,
treatment with IFNb and GA was not initially recommended
by the National Institute for Clinical Excellence (NICE) due
to unacceptably low levels of cost-effectiveness (National
Institute for Health and Clinical Excellence, 2002), but
subsequently were included via a special and controversial
risk-sharing plan designed to lower costs. These treatment
options are also offered in Australia and New Zealand
(Raftery, 2008), but there is ongoing debate about the
soundness of these policies (McCabe, 2010).
3. Epidemiology
The geographical distribution of MS is very heterogeneous
and has been studied and discussed widely. It is well
established that MS prevalence has a latitudinal gradient;
that is, that MS prevalence grows as one moves farther from
the equator. Colombia is in a low-risk region because of its
localization on the equator (Kurtzke, 1975). In this section
we discuss the epidemiology of MS in Colombia vs. other
South American countries, particularly neighboring coun-
tries near the equator.
Colombia lies in the northwest region of South America,
bordered on the north by the Caribbean Sea and on the west
by the Pacific Ocean, and extending south and east to the
Amazon basin and the Orinoco basin, respectively. It is
crossed by the north end of the Andes range, which splits
into three smaller ranges (east, central, and west). The
country is divided in five regions that vary in climate and
altitude: the Andean, Pacific, Amazon, Caribbean, and
Oriental regions. Most of the urban population is in the
Andean region.
There are only two studies published on prevalence of MS
in Colombia. Sa nchez and colleagues used the capture–
recapture method to estimate MS prevalence on December
30, 1997, in the provinces of Santander (located on the
oriental range) and Antioquia, Risaralda, and Caldas
(located on the central range), all of which are at similar
altitudes and have similar climates. The prevalence for
these regions was estimated between 1.48 and 4.98 per
100,000.(Sanchez et al., 2000). These four regions equaled
26% of the total Colombian population at that time. We
estimated MS prevalence on December 31, 2002, in Bogota
to be 4.41 per 100.000 approximately. At that time Bogota
was 15% of the total Colombian population (Toro et al.,
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83
2007). All the cases noted by Sa nchez et al. fulfilled the
Poser criteria for MS (Poser et al., 1983). All the cases that
we registered fulfilled the McDonald criteria for MS
(McDonald et al., 2001).
The results of both studies indicate that MS is rare in
Colombia, and that Colombia can be classified as a low-risk
region for MS according to the criteria of Kurtzke (1975) .
It is important to note that the regions that were studied
are the most populous of Colombia. Within these regions lie
the two most important and populous Colombian cities,
Bogota and Medellı́n. The population of Bogota may be
representative of the entire Colombian population because
of the internal migration from all over the country. How-
ever, the prevalence of MS in the other regions of the
country, including rural areas, has not been studied. These
findings are consistent with the view that the tropics are a
low-prevalence region for MS (Kurtzke, 1975; Pugliatti
et al., 2002). They are also in agreement with the low
estimated prevalence of MS in neighboring countries.
In Mexico, the prevalence of MS in the city of San Pedro
Garza Garcı́a (located in the northeast, along the USA
border with the state of Texas) is estimated to be 30 per
100,000 inhabitants (De la Maza Flores and Arrambide
Garcı́a, 2006). In Mexico City the prevalence was 1.6 per
100.000 on January 1, 1968 (Alter and Olivares, 1970). In
the French West Indies (i.e. the islands of Martinique and
Guadeloupe) a crude MS prevalence of 14.8 per 100,000 was
calculated on December 31, 1999 (Cabre et al., 2005).
A study performed in 2007 in the city of Lima (Perú)
provided a prevalence of 7.64 per 100,000 (Vizcarra
Escobar et al., 2009). Another study in Uruguay reported
an MS prevalence of 30 per 100,000 (Oehninger et al.,
1998). In Chile a prevalence of 5.69 per 100,000 was
reported recently (Melcon et al., 2012).
As of July 2005, the prevalence of MS in Panama was
estimated to be 5.24 cases per 100,000 inhabitants (Gracia
et al., 2009). In Quito, the capital of Ecuador, the pre-
valence of MS was estimated to be 5.05 cases per 100,000 in
2006. In two other major Ecuadorian cities, Cuenca and
Guayaquil, the prevalence rates for MS was of 0.75 cases per
100,000 and 2.26 cases per 100,000, respectively (Abad
et al., 2010). Some studies of sub-Saharian Africa and
southern Asia, which are at the same latitude as Colombia,
indicate a similarly low prevalence of MS (Kurtzke, 1975;
Pugliatti et al., 2002; Kioy, 2001). By contrast, MS is more
prevalent in South American countries located farther from
the equator, especially Brazil and Argentina. MS prevalence
in Sa~ o Paulo was estimated by Callegaro et al. (2001) to be
15.0 cases per 100,000 inhabitants for 1997. They noted a
3-fold increase in MS prevalence over a 7-year period
following their initial estimate (Callegaro et al., 1992),
but it is reasonable to assume that this discrepancy reflects
diagnostic difficulties in the first study as opposed to a real
increase in prevalence. Similar estimates were obtained in
the cities of Londrina and Arapongas (Kaimen-Maciel et al.,
2004), which lie approximately 600 km to the west of Sa~ o
Paulo. Reports for MS prevalence in other Brazilian cities
have been published: Cuiaba 15 per 100,000 (Melcon et al.,
2012), Belo Horizonte 18.1 per 100,000 (Lana-Peixoto et al.,
2012), Botucatu 17 per 100,000 (Rocha et al., 2002), Santos
15.5 per 100,000 (Fragoso and Peres, 2007), Rio de Janeiro
5 per 100,000 (Alvarenga et al., 2000) and Recife 1.36 per
84
Figure 1 Prevalence of multiple sclerosis (MS) among Latin American countries and Colombian cities.
100,000 (Ferreira et al., 2004). In Argentina prevalence
estimates range from 13.4 to 21.5 cases per 100,000
inhabitants, depending on the city surveyed, indicating that
the entire country is a medium-risk region (Cristiano et al.,
2009; Melcon et al., 2008).
As expected because of latitudinal gradient, the incidence
of MS was higher in the southern cone, as shown by Cristiano
et al. (2010), who estimated disease incidence of 1.76 cases
per 100,000 inhabitants per year, and by Dı́az et al. (2012) who
found an incidence of 0.90 cases per 100,000 inhabitants per
year in Chile. These findings are both higher than those found
in Panama by Gracia et al. (2009). However, a study performed
in the French West Indies after return migration of the
population, calculated a crude mean annual MS incidence of
1.4 per 100,000 inhabitants, for the period between July 1,
1997, and June 30, 2002. The French West Indies comprise two
islands, Martinique and Guadeloupe, both situated in the
Caribbean basin at latitudes between 14130 N and 161N.
Martinique showed a higher incidence (two per 100,000) than
Guadeloupe (0.7 per 100,000) (Cabre et al., 2005). It is
worth noting that these findings support the hypothesis of
certain environmental factors serving as triggers for the
development of MS.
Collectively, these studies confirm the oft-described
latitudinal gradient of MS frequency in South America. This
is clear in the comparison of findings from southern coun-
tries such as Argentina, Chile, and Brazil with countries on
the equator. The gradient could be taken support the
hypothesized role of ultraviolet radiation and vitamin D
levels in MS pathogenesis (Ascherio, 2010), but further
studies on this topic are needed. However, the populations
of the two regions (southern vs. equatorial South America) have
different genetic backgrounds stemming from different waves
of immigration, particularly from European countries other
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J. Toro et al.
than Spain (mainly Italy and Germany), which took place in
the second half of the 19th century and the early decades of
the 20th century (Sa nchez-Albornoz et al., 1968). This issue
will be discussed in Section 4
The latitudinal gradient of MS frequency is not as clear within
countries as it is between countries. However, this could be due
to factors unrelated to MS risk or etiology such as internal
migration, access to health care services for diagnosis or
treatment, and disability-related issues. The only study to
provide evidence for a latitudinal gradient within a country
found that MS incidence in the Magallanes region of Chile (the
southernmost region of the country) is almost four times that of
the country as a whole (Dı́az et al., 2012).
Although there have been some reports which show that
the prevalence of MS among persons born in regions with
higher altitude to be greater than those born in lower
regions (Cernacek et al., 1971) this is not the case in Latin
America. Furthermore a study published by Norman et al.
(1983) shows that altitude does not affect the risk of MS
when adjusted for latitude of birth place.
The frequency of MS in other regions of South America is
unknown. Definitive prevalence studies are needed
in countries such as Paraguay, Bolivia, and Venezuela, and
in secondary cities and rural regions of most South American
countries. Figure 1 summarizes the different MS prevalences
among some Latin American countries and highlights the MS
prevalence for several Colombian cities.
4. Genetics
MS is believed to develop in genetically susceptible people
when triggered by an environmental factor. The genetics of
Multiple sclerosis in Colombia and other Latin American Countries
MS have been studied intensively in many high-prevalence
countries, but not in Latin America.
The Colombian population is genetically heterogeneous,
with Native American, European, and African (primarily sub-
Saharan) origins. Colombia was the first South American region
conquered by the Spanish in the 15th century (Sa nchez-
Albornoz et al., 1968). Prior to that Colombia was inhabited
by native populations with a relatively homogeneous genetic
background. The maternal lineage of the modern Amerindian
populations in Colombia is distributed equally among the
major Amerindian mitochondrial haplogroups A, B, and C,
with a low frequency of haplogroup D. However, this distribu-
tion is disrupted by the Andes, which divide the Amerindian
population in two, one resembling the central and North
American populations to the north and west of the range, and
the other resembling South American populations to the south
and east of the range (Keyeux et al., 2002; Melton et al., 2007).
The genetic background of the indigenous population was
blurred by the arrival of the Spanish conquerors, which also
brought African slaves. The three populations have shared
the region since then, and there has been significant
mixing among them. The most common is the admixture
of Caucasian men and native women, called mestizos
(Sa nchez-Albornoz et al., 1968). Modern admixed popula-
tions, such as Mestizos, Mulattos (from the admixture of
Caucasian men and African women), and Afro-Colombians,
share their ancestry with Native American and Sub-Saharan
African populations (Salas et al., 2008; Rodas et al., 2003).
Because the Colombian population is so genetically
heterogeneous, it is difficult to study genetic associations
with complex diseases such as MS. Mesa and colleagues
studied autosomal, Y chromosomal, and mitochondrial DNA
markers of different populations in Colombia, including
native tribes (Mesa et al., 2000). They found that mating
occurred predominantly between male conquerors and
female natives. A similar finding was reported by Carvajal-
Carmona (Carvajal-Carmona et al., 2000), who showed that
a specific Colombian population living in the province of
Antioquia has been genetically isolated throughout the
history of the country and has an important contribution
from Jewish populations. This is the only population in
Colombia in which the genetics of MS have been studied.
Sa nchez also studied the association of MS with human
leukocyte antigen (HLA)–DQ alleles in a sample of 32 MS
patients from Antioquia (Sa nchez et al., 2000). They found a
significant protective association with the HLA-DQ3 allele.
Palacio studied linkage disequilibrium of the 6p chromosome
using STR microsatellites (Palacio et al., 2002). They found an
association between MS and certain polymorphisms of the
microsatellite loci D6S276 and D6S273, suggesting that the
region 6p21.3–21.4, which contains HLA and tumor necrosis
factor (TNF) genes, is associated with MS in this population.
More recently, Rojas conducted a case–control study in which 65
patients were matched with 184 healthy controls (Rojas et al.,
2010). They typed HLA-DRB1 alleles and found a significant
association between MS and alleles HLA-DRB1n0103 and HLA-
DRB1n15. Interestingly, they found a protective association
with the alleles HLA-DRB1n0301 (OR: 0.512; CI: 0.29–0.906)
and HLA-DRB1n0703 (OR: 0.264; CI: 0.079–0.883). Because
these three studies were restricted to MS patients from
Antioquia, their findings might not be representative of the
entire population of Colombia.
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85
Importantly, Rojas et al. (2010) did not find an association
between MS frequency and HLA-DRB1n1501, which is the
allele most consistently associated with MS worldwide
(Schmidt et al., 2007; Hafler et al., 2007; Esposito et al.,
2010), including Latin American countries such as Mexico
(Ala ez et al., 2005) and Brazil (Alves-Leon et al., 2007;
Kaimen-Maciel et al., 2009). Likewise, in Bogota we found
no association of the HLA DRB1n15 allele with MS. However,
a significant protective association with the HLA DRB1n14
allele was noted (unpublished data). Brum and colleagues
also found a protective effect of HLA DRB1n14 in their
analyses of a mixed population as well as white and mulatto
populations independently (Brum et al., 2007). Collectively,
these findings may indicate that the Native American
genetic background of the South American population
carries protective alleles that are at least partly responsible
for the low prevalence of MS in the tropical countries of South
America. However, this protective association has been found
in Caucasian populations as well, leaving this issue unresolved
(Barcellos et al., 2006; Dyment et al., 2005).
The association of MS with HLA alleles other than
DRB1n01 is yet to be clearly defined. Alves-Leon et al.
(2007) showed that black and white populations are geneti-
cally independent and that genetic associations with MS in
the two populations are different. This racial difference has
not been studied in Colombia, most likely because black MS
patients are very scarce in Colombia. In fact, none of the
three published Colombian studies reported the proportion
of black patients in their populations, and we have no
knowledge of any black MS patients in Bogota .
5. Clinical course
Traditionally, MS has been described as a chronic medical
condition predominantly affecting Caucasian people in
developed countries. Nevertheless, recent studies in coun-
tries outside of high-prevalence regions suggest that MS is
not as uncommon in Latin America and other low-frequency
zones as once thought. An increasing number of studies have
appeared since the 1990s, most of them coming from Brazil.
In a retrospective study in Rio de Janeiro, 122 MS patients
were identified since 1978 (Alves-Leon et al., 2008). They
described the most common symptoms and clinical features
seen in their populations and compared their observations
with those of other Brazilian studies. The majority of the
patients were female (70%) and Caucasian (67%). There
were pyramidal symptoms in 42.4% of the patients, sensory
loss in 14.1% of the patients, and brainstem dysfunction in
12% of the patients. Interestingly, visual symptoms (6.2%)
were not as common as in other studies (Alves-Leon et al.,
2008). Table 2 describes the clinical features of MS patients
in studies done in Latin America.
Few studies have examined the clinical spectrum of MS in
Colombia. Sa nchez et al. (2001), analyzed 65 Caucasian
patients with definite MS, described the frequency of clinical
manifestations in this population, and compared them with
another series from temperate zones. Most patients (69.2%)
had RRMS; the remainder (31.8%) had chronic-progressive MS
(CPMS). As many as 60% of patients reported only one
symptom before MS was diagnosed. The frequency of motor
disturbances was 35.7%, while optic neuritis was seen in 46.4%
86 J. Toro et al.

Table 2 Studies of multiple sclerosis in Latin America.

Authors and country Number of Clinical subtypes Symptoms at disease onset

patients

Arruda et al. (2001)
(Brazil)
Alves-Leon et al. (2008)
(Brazil)
Vizcarra-Escobar et al.
(2005) (Peru)
Herna ndez-Valero et al.
(2004) (Cuba)
Tilbery et al. (1995)
(Brazil)
Toro et al. (2007)
(Colombia)
200 91% RRMS, 8% PPMS, 1% SPMS Brainstem/cerebellar 63%, sensory 53%, motor
49.5%, optic neuritis 39.5%
122 69.6% RRMS, 13.1% PPMS, 17.2% SPMS Brainstem/cerebellar 8%, sensory 23%, motor
24%, visual 14%
55 49.1% RRMS, 20% PPMS, 12.7% SPMS, Sensory 33%, motor 35%, optic neuritis 36%
12.7% PRMS 5.5% CIS
50 74% RRMS, 12% PPMS, 14% SPMS Brainstem/cerebellar 42%, sensory 44%, motor
44%, visual 52%
214 82% RRMS, 18% PPMS Brainstem/cerebellar 32%, sensory 27%, motor
47%, visual 27%
224 75.7% RRMS, 3% PPMS, 6.4% SPMS, N/A
1.3% PRMS, 10% UN

RRMS, relapsing/remitting multiple sclerosis; PPMS, primary progressive multiple sclerosis; SPMS, secondary progressive multiple
sclerosis; PRMS, progressive relapsing multiple sclerosis; CIS, clinically isolated syndrome; UN, unclassified.

of the population. Of particular interest was the analysis of
the patient’s extended pedigree, which failed to identify
relatives affected by MS or a similar disease (Sa nchez et al.,
2001). This finding contrasts with that of a European study in
which MS incidence was increased among relatives of afflicted
people (Sadovnick et al., 1988).
In general, the clinical spectrum of MS in Latin America is
similar to that in high-prevalence regions. Visual, brain-
stem, motor, and sensory domains are involved most
commonly. The relative frequencies may vary, even within
a country, but there is no evidence that might suggest any
systematic difference in the clinical presentation of MS in
Latin America vs. high-prevalence regions (Alves-Leon
et al., 2008; Finkelstein A et al., 2009).
Besides clinical symptoms, other characteristics have
been studied, such as clinical subtypes, progression, and
demographic factors. The most frequent type of MS is RRMS,
similar to Europe or the United States. PPMS is usually seen
in 10% to 15% of most series worldwide; however, almost all
of these series are from the United States, Europe or
Australasia. PPMS is different from RRMS in several ways.
PPMS tends to affect older people and has a male-to-female
ratio of 1:1. The majority of PPMS patients develop motor
disturbances related to spinal cord involvement, with a high
progression rate (Bashir et al., 1999). The frequency of
PPMS reported in Latin American countries varies between
8 and 18% in Brazil (Arruda et al., 2001), is 20% in Peru
(Vizcarra-Escobar et al., 2005) and is 8% in Western Cuba
(Hernandez-Valero et al., 2004). In Colombia, although no
studies specifically address this question, it is important to
note that in Bogota , the proportion of patients with PPMS
was only 3% among a population of 296 cases (Toro et al.,
2007). This could suggest a differential incidence of PPMS
in different populations, but this finding must be confirmed
in future investigations.
In a Brazilian study examining the progression of MS,
Ferreira Vasconcelos et al. (2010) described differences in
disease progression and disability in PPMS patients
of different ethnicities. They found that the progression of
MS was particularly rapid and severe in Brazilian patients
of African origin, consistent with findings of American and
European studies of patients of African descent (Jeannin
et al.,2007), suggesting that race may play a greater role
than environment in the progression of MS (Ferreira
Vasconcelos et al., 2010). There is not enough information
available to compare the clinical presentation of MS
patients in Latin America with the rest of the world in
terms of male-to-female ratio, age of onset, or secondary-
progressive forms (Vasconcelos et al., 2006).
A few studies have described CSF characteristics of MS
patients in Latin America and other parts of the world. The
proportion of patients with positive oligoclonal bands in
Latin American studies(Puccioni-Sohler et al., 1999) is quite
similar to that seen in studies in high-prevalence zones
(Bourahoui et al., 2004). There are no important regional
differences in other CSF findings (Puccioni-Sohler et al.,
1999; Ferreira Vasconcelos et al., 2008).
A differential diagnosis that one must consider is HTLV-1-
associated myelopathy/tropical spastic paraparesis (HAM/
TSP). This insidious inflammatory chronic myelopathy is
caused by the Human T Cell Lymphotropic Virus Type 1
(HTLV-1). It is usually progressive and can mimic a primary
progressive multiple sclerosis (PPMS) (Keegan, 2011). HTLV-1
is a retrovirus that can be transmitted sexually, by sharing
contaminated needles, blood transfusions and through
breast feeding from mother to child (Goncalves et al.,
2010). The highest prevalence rate for HTLV-1 includes
south western Japan, several sub-Saharan African countries,
Central and South America and some areas of Iran and
Melanesia (Carneiro-Proietti et al., 2006). All 13 South
American countries have reported the presence of HTLV-1,
but the prevalence varies greatly from less than 0.1–5%. The
highest proportion of infection among the general popula-
tion (1–5%) has been reported in Brazil, Colombia and Perú.
On the other hand, HTLV-1 appears to be uncommon in
central and southern Argentina and in Venezuela. HTLV-1 is
seen more frequently in tropical, developing areas, in
African-American population such as individuals in the state
of Bahia in Brazil, French Guiana, Guyana, Suriname, the
Pacific coast of Colombia (Tumaco city) (Arango et al., 1988;
Roma n and Roma n, 1988; Zaninovic et al., 1988) and Peru
(Chincha province) (Carneiro-Proietti et al., 2002, 2006;

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Multiple sclerosis in Colombia and other Latin American Countries
Gotuzzo et al., 2000). Unfortunately neither pregnant
women nor blood donors are routinely screened for HTLV1
in Colombia.
It has been suggested that approximately 0.2–5% of HTLV-
1 carriers develop HAM/TSP. In general, the onset of HAM/
TSP is in the fourth to fifth decade of life (Carneiro-Proietti
et al., 2006; Gotuzzo et al., 2000; Proietti et al., 2005).
HAM/TSP is clinically characterized by spastic paraparesis
and gait disturbance, frequently associated with sensory
and bladder dysfunction. The myelopathy is usually thoracic
with the MRI showing spinal cord atrophy and non-enhancing
T2 lesions. The diagnosis is based on the clinical and
radiologic findings and the presence of Western blot con-
firmed HTLV-1-specific antibodies in the serum and CSF
(Engstrom, 2011; Gotuzzo et al.,2000; Keegan, 2011;
Wingerchuk, 2012). Up to now, no treatment for HAM/TSP
has proven to be effective consistently and in the long term.
Neuromyelitis optica (NMO) is another differential diag-
nosis that one must consider. Although in HAM/TSP there
have been some case reports in which patients develop
optic neuritis, this is extremely unusual (Komaba et al.,
1996; Yoshida et al., 1998). There are only two reports
published of prevalence of NMO in Latin America and the
Caribbean. In Cuba a study showed a prevalence of 0.52/
100,000 inhabitants and an annual incidence of 0.053/
100,000 (Cabrera-Gomez et al., 2009). In the French West
Indies the prevalence of NMO was of 4.2/100,000 inhabi-
tants and the mean annual incidence for the period July
2002 to June 2007 was 0.2/100,000 (Cabre et al., 2009).
In Colombia and many countries of South America reference
laboratories are used for measurements of anti NMO
antibodies.
The growing literature on the regional prevalence of MS
contributes to our understanding of the clinical profile and
evolution of MS in Latin American countries, particularly
when considering that there are different prevalence zones
within Latin America itself.
Conflict of Interest
The authors have nothing to declare.
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