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ORIGINAL CONTRIBUTIONS

Received: November 2^nd 2015

Judged: May 2^nd 2015

Clinical and demographic characteristics of patients with multiple sclerosis

Brenda Bertado-Cortés,^a Lyda Villamil-Osorio,^a Raúl Carrera-Pineda,^a Carlos Martínez-Cortés,^a José Guerrero-Cantera^b

^aServicio de Neurología

^bUnidad de Investigación Médica en Enfermedades Neurológicas

Hospital de Especialidades, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Ciudad de México, México

Communication with: José Guerrero Cantera

Email: neurojgc@gmail.com

Background: Multiple sclerosis (MS) is a disease whose physiopathogenesis shows a complex interaction of genetic and environmental factors. Given that those factors have not been documented in our country, we describe the clinical and demographic characteristics from a sample of patients with MS.

Methods: We carried out an observational, descriptive, cross-sectional, and retrolective study in a Center for Demyelinating Diseases. We took the information from the clinical records of a sample of patients with multiple sclerosis, who arrived to the center from April 2014 to July 2015.

Results: We obtained data from 313 patients, out of which 65.5 % were women. Mean age was 41 years (SD 11.22). Minimum age of diagnosis was 12 years and maximum, 66 years; mean age of diagnosis was 32 years (SD 9.72). With regards to clinical variables, 3.4 % presented radiologically isolated syndrome (RIS), 82 % relapsing-remitting MS (RRMS), 13.9 % secondary-progressive MS (SPMS), and 0.8 % primary-progressive MS (PPMS). Of all the patients, 10 % had first or second degree relatives with diagnosis of this disease; 16 % had foreign ancestors; 27 % were smokers. Treatment consisted of glatiramer acetate, 28 %; intramuscular interferon beta 1a, 18 %; subcutaneous interferon beta 1a, 16 %; subcutaneous interferon beta 1b, 30 %; fingolimod, 3 %; and others, 5 %.

Conclusions: Clinical and demographic characteristics are similar to those reported in international literature. More studies would be needed to typify Mexican population with MS.

Keywords: Multiple sclerosis; Epidemiology

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Multiple sclerosis is an inflammatory, chronic, demyelinating disease of the central nervous system (CNS), considered autoimmune, with a complex interplay of genetic and environmental factors in its pathogenesis.^1,2 It has been reported that the disease is not likely the result of a single causal event, and it seems to develop in genetically susceptible populations, as the result of environmental exposures.³

In multiple sclerosis the precise etiological determinants of onset and clinical course remain poorly understood; however, in the search for greater understanding of what constitutes the risk of the disease or more severe clinical courses, epidemiology has been invaluable in efficiently clarifying key behavioral, environmental, and genetic factors that modulate risk, including the role of Epstein-Barr virus (EBV), ultraviolet radiation, levels of vitamin D, tobacco use, and the HLA-DR1 locus within the major histocompatibility complex (MHC).⁴

The number of people with MS in the world has risen. It is estimated to have increased from 2.1 million in 2008 to 2.3 ​​million in 2013, and the overall prevalence went from 30 per 100,000 inhabitants in 2008 to 33 in 2013.⁵ In Mexico, publications of hospital and population studies show an increase in the prevalence of multiple sclerosis: in northern Mexico they say that there are 13 cases per 100,000 inhabitants; however, these data only consider the insured population in that region.⁶

Several factors associated with multiple sclerosis have been identified, such as genetic associations, ethnic origin (the disease is more common in the Caucasian population), greater affliction in women, smoking, exposure to certain infectious agents (Epstein Barr virus), vitamin D deficiency, latitude, and others.

This study aims to identify and describe demographic and clinical characteristics of patients diagnosed with multiple sclerosis treated at the Hospital de Especialidades del Centro Medico Nacional Siglo XXI.

Methods

An observational, descriptive, transversal and retrolective study was done in the Demyelinating Diseases Clinic of the hospital mentioned. Information was obtained from clinical records of a sample of patients collected in the clinic census from April 2014 to July 2015. Records of adult patients with the diagnosis of multiple sclerosis according to the 2010 McDonald criteria were included. The study was approved by the Local Research Committee. 

Data were obtained directly from records and culled in forms designed for this purpose; then they were filled into an electronic database.

Age, gender, month of birth, age at diagnosis, clinical phenotype of multiple sclerosis, family history of this disease, and foreign descent (presence of an ancestor born in a country other than Mexico from whom the patient was descended) were collected as the main variables for this study.

Quantitative variables were summarized as mean and standard deviation, the qualitative variables as frequency and percentage. Data were presented in tables. For statistical analysis the program SPSS, version 21 was used.

Results

Data from 313 patients were obtained, although not all records may have information on all variables. The mean age of patients was 41 years (SD 11.22); 108 were men (34.5%) and 205 women (65.5%). The mean age at diagnosis was 32 years (SD 9.72); the most common range was between 21 and 30 years (32.9%) and 31 to 40 (34.5%). It was found that the minimum age of diagnosis of multiple sclerosis was age 12, and the maximum age was 66. The diagnosis was made before age 20 in 41 patients (13.1%) and after age 40 in 61 patients (20%). 27% of patients smoked (n = 270) and 43% had other diseases (n = 247) (Table I).

The birth month of patients was recorded and there was a very homogeneous distribution, which rose slightly in August, with 10.9%. 32 patients (11%) had a relative affected by multiple sclerosis, which were grandparents in 0.4%, parents in 1.1%, siblings in 3.4%, uncles and aunts in 1.5%, cousins in ​​3.7%, and nephews and nieces in 0.8%. 16% had an ancestor born abroad, mainly in Europe (Norway, England, France, Scotland, Germany) and in other countries of the Americas; those relatives were most often grandparents. 87% of patients were from Mexico City (Table II).

Patients were classified according to clinical phenotype: 260 had the relapsing-remitting variety (RRMS) (83.1%), nine had the clinically isolated syndrome (CIS) (2.9%), two had the primary progressive form (0.6%), and 42 had the secondary progressive form (SPMS) (13.4%) (Table III). Patients with the RRMS clinical phenotype had an average age of 39.2 years (SD 9.78), and the average age at diagnosis was 31.3 years (SD 9.54); the average age of patients with the PMSC clinical phenotype was 53.35 years (SD 13.61), and the average age at diagnosis of multiple sclerosis was 36.46 years (SD 11.77); the average age of patients with CIS was 36.89 years (SD 6.25) and the average age at diagnosis 32.11 years (SD 4.54). In the case of PPMS, the average age was 56 (SD 11.31), and at diagnosis 46.5 (SD 6.36).

With respect to modifying treatments for the disease that patients received, 28% received glatiramer acetate, 30% interferon beta-1b, 18% interferon beta-1a IM, 16% interferon beta 1b SC, and 3% received other treatments (Table IV).

Discussion

Multiple sclerosis is more common in women than in men:1,3 in our sample of 313 patients, we found that 65.5% were women and 35.5% men, for a female: male ratio of 1.8:1. This ratio is lower than in other populations, as in Europe, for example, where there are ratios of 4:1. Studies have not found any convincing justification for the association between genes involved in the disease and the X chromosome.³

The patients studied are aged between 19 and 79 years, with an average age of 41. The minimum age at diagnosis was 12 years old and the maximum age 66 years, with an average age at diagnosis of 32 years, which is consistent with data indicating that multiple sclerosis mainly affects young people and begins usually between 20 and 50 years, with an average age of onset at 30 years. In our study, patients diagnosed between 21 and 50 years accounted for 84%, and disease onset was less frequent before age 20 (13%) and after age 51 (3%). According to the phenotype, RRMS had a mean age at diagnosis of 31.3 years and PFMT of 46.5 years, which is consistent with reports in the literature.     

Some references have tried to establish whether the birth month influences the risk of developing multiple sclerosis. It has been noted that north of the Equator, individuals born in May have a 9.1% higher risk of developing multiple sclerosis when compared to a risk below 8.5% for those born in November.³ Although the effect of birth month on the risk of this disease has been reported in numerous groups, and this in turn may influence future risk of the disease,⁷ in our population that risk does not appear to be likely or of high value, since the distribution of birth months is very similar and there only appears to be a higher percentage in August (10.9%); however, this is not significant compared to other months with great homogeneity with percentages between 7 and 8%; this contrasts with information from a country like Scotland, which has 31% more births in April and 20% fewer births in November.³ However, this result may also be due to not adjusting for the year and place of birth of each patient, as has been done in some Norwegian and Canadian cohorts or other studies; also there is no data from the southern hemisphere, which is noted for having more diagnoses of multiple sclerosis in people born in November-December compared to those born between May and June.⁸ Our data are similar to those of Australian and Italian patients, in which it was reported that birth month confers no risk factor for the development of multiple sclerosis.

10% of patients have a first, second, or third degree family member with the diagnosis of multiple sclerosis, a smaller percentage than described, as the risk varies by race and geographic region,⁹ and about 20% of patients with this disease in Europe have a first-degree relative with the same diagnosis.¹⁰

It is described that parents often have a recurrence risk rate (RRR) of 3%;¹⁰ however, in our population parents were 1.1%, and sons or daughters with the disease were not reported. In the case of siblings, a 4% RRR is described, and our study found 3.4% of the total sample with a sibling with the diagnosis. For uncles and aunts an RRR of 2% is described, and our sample found 1.5% of patients with a history of aunts with this disease. For nephews and nieces there is mention of a 2% RRR, and we found 0.8% with nephews and nieces with the diagnosis. In the case of cousins ​​we found 3.7% with a history of diagnosis, with an RRR of 1% described in the literature. Future studies must associate risk factors in order to determine the recurrence risk rate in relatives and describe whether the clinical phenotypes are similar or different.

16% of patients in our sample had foreign ancestry, and 82% of foreign families came from Europe, mostly Spanish. 6% came from the Americas and 7% from Asia. European countries from which foreign ancestors originated were Spain, Norway, England, France, Scotland, and Germany, all with a prevalence of the disease over 100 cases per 100,000 population, suggesting a high genetic condition; however, this cannot be established clearly.

87% of our patients are from Mexico City, as this population has enrollment and greater access to the Demyelinating Diseases Clinic at Centro Médico Nacional Siglo XXI.

The most recognized clinical presentation in the literature due to its development and clinical manifestations is the RRMS phenotype, which, although there are still no studies that take into account the current classification (2014), in the previous data the outbreak-remission phenotype was more frequent, similar in our population, as 83% of patients had this clinical phenotype. It is also described that the least common phenotype is PPMS, and in our population only 0.6% has this phenotype.

A positive association was found between cigarette smoking and the risk of developing multiple sclerosis, with a relative risk of 1.6 for individuals with a significant smoking history.¹¹ Smoking may also negatively influence the progression of the disease, as it accelerates the transition from RR to SP, and in turn subjects who smoke are twice as likely to develop primary progressive multiple sclerosis when compared to nonsmokers with multiple sclerosis.¹¹ In addition, a relationship has also been observed between smoking and outbreaks. Our sample found that of the 270 patients for whom this information was obtained, 27% were smokers. 

We recognize that there are several variables of clinical and epidemiological interest that were not included in this analysis; despite this, the results are useful to begin to characterize patients with multiple sclerosis in Mexico.

Conclusions

The characteristics reported in this study show an overall profile of patients with multiple sclerosis in a referral hospital, and can serve as a basis for future research that can combine all variables and apply the equations designed globally to establish prevalence, as well as genetic and environmental relationships.

References

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