Demographic, clinical and comorbidity data in a large sample of 1147 patients with migraine in Mexico City

Abstract

The objective was to identify the sociodemographic and clinical characteristics of a large sample of patients with migraine in Mexico City. This cross-sectional study was performed in two tertiary centers in Mexico City and affiliated hospitals. We evaluated the presence of migraine through a standardised interview according to the criteria of the International Headache Society. We studied 1147 patients. The mean age was 37.1+/-13.6 (6-77) years. Nine hundred and twenty one patients were female (80%). The age of onset of migraine was 19.4+/-10.3 (1-69) years. Six hundred and four patients had migraine with aura (53%) and 543 without aura (47%). The female/male ratio was 4:1. One hundred and forty-seven patients had cardiovascular problems (13%), 72 had neurological problems (6%), 233 had gastrointestinal problems (20%) and 323 had psychiatric problems (28%). In this study we described the clinical characteristics of a large sample of patients with migraine in Mexico City. Our sample has similar characteristics to other countries. [PUBLICATION ABSTRACT]

J Headache Pain (2005) 6:128134

DOI 10.1007/s10194-005-0167-0ORIGINALJos F. Tllez-Zenteno

Guillermo Garca-Ramos

Fernando Zermeo-Phls

Antonio Velazquez

GGSMDemographic, clinical and comorbidity data

in a large sample of 1147 patients

with migraine in Mexico CityAbstract The objective was to

identify the sociodemographic

and clinical characteristics of a

large sample of patients with

migraine in Mexico City. This

cross-sectional study was performed in two tertiary centers in

Mexico City and affiliated

hospitals. We evaluated the

presence of migraine through a

standardised interview according

to the criteria of the International

Headache Society. We studied

1147 patients. The mean age was37.113.6 (677) years. Nine

hundred and twenty one patients

were female (80%). The age of

onset of migraine was 19.410.3

(169) years. Six hundred and

four patients had migraine with

aura (53%) and 543 without aura

(47%). The female/male ratio was

4:1. One hundred and forty-seven

patients had cardiovascular

problems (13%), 72 had

neurological problems (6%),

233 had gastrointestinal

problems (20%) and 323 had

psychiatric problems (28%).

In this study we described the

clinical characteristics of a large

sample of patients with migraine

in Mexico City. Our sample has

similar characteristics to other

countries.Received: 24 December 2004

Accepted in revised form: 22 April 2005

Published online: 13 May 2005J.F. Tllez-Zenteno () G. Garca-Ramos ()

GGSMDepartment of Neurology and Psychiatry,

National Institute of Medical Sciences and

Nutrition Salvador Zubirn,

Vasco de Quiroga No. 15, Colonia Seccin XVI,

Delegacin Tlalpan, Mxico,D.F. CP 14000, Mexicoe-mail: [email protected]: [email protected]. Zermeo-PhlsMigraine Clinic,National Institute of Neurology and

Neurosurgery,Manuel Velzco Suarez, MexicoA. VelazquezBlood Bank,National Institute of Medical Sciences and

Nutrition Salvador Zubirn,

Mexico City, MexicoKey words Migraine Migraine

with aura Headache Triggers

Associated conditions Tertiary

centre Developing countries Migraine clinicIntroductionEpidemiology has several important implications for the

diagnosis and treatment of migraine. Migraines prevalence and distribution in different countries and its

impact on individuals and on societies needs to be

addressed. Examination of sociodemographic, familial

and environmental risk factors helps to identify the

groups at highest risk for headache and may ultimately

provide clues to preventive strategies or mechanisms of

the disease [1]. At the present time clinical studies of

migraine are more reliable because they use the criteria of

the International Headache Society (IHS), which are

more complete, explicit and rigorous than the criteria that

were used in previous studies [24].129Migraine prevalence varies by age and gender. Before

puberty, migraine prevalence is higher in boys than in

girls; then the prevalence increases more rapidly in girls

than in boys as adolescence approaches [5, 6]. Prevalence

increases until approximately age 40, when it declines [7,8]. The gender ratio also changes with age. Cyclical hormonal changes associated with menses may account for

some aspects of the migraine prevalence ratio. However,

hormonal factors cannot account for all of the gender differences; prevalence remains substantially higher in

women than men, even at 70 years of age, well beyond the

time that cyclical hormonal changes may be considered a

predisposing factor [9].Migraine is comorbid with a number of neurological

and psychiatric disorders. Understanding the comorbidity

of migraine is potentially important from a number of different perspectives. First the occurrence of comorbidity

has implications for the diagnosis of headache because

migraine has a substantially symptomatic overlap with

several of the comorbid conditions, for example migraine

and epilepsy can cause transient alterations of consciousness as well as headache. Second, comorbidity has important implications for treatment. Comorbid conditions may

impose therapeutic limitations, but may also create therapeutic opportunities. For example, when migraine and

depression occur together, an antidepressant may successfully treat both conditions. Finally the study of comorbidity may provide epidemiological clues to the fundamental

mechanism of migraine [10].The American Migraine Study [9] found that approximately 23 million Americans suffered severe migraine;

more than 85% of women and 82% of men with severe

migraine had a headache-related disability. This is a

chronic disorder that usually accompanies the patient

from his diagnosis through the rest of his life.

Epidemiological information in developing countries is

scant and is necessary because risk factors and social attitudes toward migraine can be identified, which may influence health care. In this study we described the characteristics of a large population of patients with migraine that

were prospectively included in a genetic study exploring

clinical characteristics and comorbidity.ResultsGeneral descriptionWe studied 1147 patients. Mean age was 37.113.6 years

(677). Nine hundred and twenty-one patients were

female (80%) and 226 male (20%). The age onset of

migraine was 19.410.3 years (169). The majority of

patients had nausea during the episodes of headache

(88%), phonophobia (80%) and photophobia (92%). In

the analysis by gender, males had an early onset of

migraine, higher height and weight and higher frequency

of alcoholism and smoking habit. Six hundred and four

patients had MA (53%). The rest of the characteristics are

shown in Table 1.Materials and methodsThis cross-sectional study was performed at the Neurology

Department of the Instituto Nacional de Ciencias Mdicas y

Nutricin Salvador Zubirn (INCMNSZ) and the Migraine

Clinic of the National Institute of Neurology. These hospitals are

national reference centres for different neurological diseases in

Mexico. The study was approved by the local Institutional

Review Board of the two institutions. The data collection was

performed between March 2003 and July 2004. Patients with

known secondary causes of headache and patients who declined

the interview and the clinical examination were not included.

Patients were approached for consent to participate in our study

in a consecutive manner. Through a standardised interview

according to the criteria of the IHS and a physical examination

performed by a physician, we evaluated the presence of

migraine. The headache test uses 49 questions and classifies

headache into migraine with aura (MA), migraine without aura

and tension headache; it also assesses the type and frequency of

pain medications used for the treatment of headache. For this

study we only used the migraine section. It has been previously

tested in a healthy Mexican population [1113]. This questionnaire measures some sociodemographic data and disability. All

previous or present disease manifestations were recorded from

patients clinical files and with a clinical interview. A blood sample was taken from all patients to perform a genetic analysis

(these results will be available at the end of 2005). We used the

MIDAS questionnaire to evaluate headache-related disability[14]. The presence of migraine in the last year was ascertained

according to the validated questionnaire [11]. The percentage of

patients who refused to participate was 5%.Statistical analysisA descriptive analysis was used in accordance with the level of

measurement of the variables. Patients were grouped according to

the presence or absence of aura, to compare several sociodemographic, clinical and morbidity characteristics. Mann-Whitney or t-test and Chi-square tests were performed to evaluate associations

with quantitative and categorical variables respectively; the significance was adjusted at p<0.05. To compare the frequency of

migraine in the different age groups we calculated the risk ratio

(RR) and its 95% CI. Statistical analysis was performed with SPSS

v10 for Windows.130Disability and comorbidityThe migraine disability scale showed 341 patients in grade I

and II (30%), 399 in grade III (35%) and 407 in grade IV

(36%). One hundred and forty-seven patients had cardiovascular problems (13%); the most frequent were hypertension in

120 patients (11%). Seventy-two had neurological problems

(6%); the most frequent was benign paroxysmal positional

vertigo (BPPV) in 28 (2%). Two hundred and thirty-three had

gastrointestinal problems (20%), functional bowel disorders

being the most frequent, in 180 (16%). Three hundred and

twenty-three patients had psychiatric problems, with depression as the most frequent in 212 (18%). Cardiovascular, neurological and psychiatric medical conditions were more frequent in females with migraine (p<0.05) (Tables 2 and 4).Risk ratio female/maleTable 3 shows the risk ratio (RR) female/male according to

different groups of age and types of migraine. TheTable 1 General description of the cohortFemales (n=921) Males (n=226) p* Total (n=1147)General characteristicsAge, meanSD 39.313.1 31.313.8 0.39 37.113.6

Age of onset of migraine, meanSD 20.110.3 16.610.9 0.001 19.410.3

Height, meanSD 157.1168.6 168.612.4 0.001 159.410.3

Weight, meanSD 63.112.0 71.814.7 0.001 64.813.7

Body mass index, meanSD 25.44.6 24.84.4 0.82 25.34.5

Migraine with aura, n (%) 494 (54) 110 (49) 0.20 604 (53)

Smoking, n (%) 184 (20) 73 (32) 0.001 257 (22)

Alcoholism, n (%) 43 (5) 26 (12) 0.001 69 (6)Accompanying symptoms, n (%)Nausea 816 (89) 187 (83) 0.01 1012 (88)

Vomiting 572 (62) 130 (58) 0.20 741 (66)

Phonophobia 543 (59) 123 (54) 0.21 921 (80)

Photophobia 480 (52) 110 (49) 0.34 1050 (92)*Comparison between males and femalesTable 2 Disability, comorbidity and triggersFemales, n (%) Males, n (%) p* Total, n (%)

(n=921) (n=226) (n=1147)Migraine disabilityGrade I and II 264 (29) 77 (34) 0.11 341 (30)

Grade III 326 (35) 73 (32) 0.38 399 (35)

Grade IV 331 (36) 76 (33) 0.51 407 (36)ComorbidityCardiovascular problems 139 (15) 8 (4) 0.001 147 (13)

Neurological problems 62 (7) 10 (4) 0.20 72 (6)

Gastrointestinal problems 214 (23) 19 (8) 0.001 233 (20)

Psychiatric problems 283 (31) 40 (18) 0.001 323 (28)TriggersStress 339 (37) 82 (36) 0.88 421 (36)

Menstruation 108 (12) 0 (0) NC 108 (9)

Food 88 (10) 14 (6) 0.11 102 (9)

Alcohol 60 (7) 16 (7) 0.39 76 (7)

Smoking 49 (5) 12 (5) 0.64 61 (5)

Food 88 (10) 14 (6) 0.28 102 (9)

Stress 339 (37) 82 (36) 0.13 421 (37)

Exercise 25 (3) 17 (8) 0.001 42 (4)

Others 11 (1) 1 (0.4) 0.06 12 (1)*Comparison between males and females. NC, not calculated131female/male RR in the whole population was 4.8 (95% CI3.84.3), in patients with migraine without aura was 3.3 (95%

CI 3.03.7) and in patients with aura was 4.4 (95 CI 4.14.9).TriggersThe main triggers were stress in 421 patients (36%), menstruation in 108 (9%), food in 102 (9%) and alcohol in 76

(7%). Exercise as a trigger was most frequent in males

(p<0.05). The other triggers are shown in Table 4.Comparison between patients with and without auraWe did a comparison between patients with and without

aura. We found differences in the clinical symptoms;

patients with aura had a higher frequency of nausea, vomiting, phonophobia and photophobia (p<0.05). The other

characteristics are shown in Table 5.DiscussionThe public health significance of migraine is often overlooked; probably because of its episodic nature and thelack of mortality due to the disorder. Migraine is, however, a frequently incapacitating disorder with considerable impact on social activities and work in the people

who suffer it, and may lead to significant consumption

of drugs.The female preponderance in migraine is consistent

across the different studies; the majority of the studies

show that migraine is more common in females than in

males with a ratio of about 1:2 to 3. Both migraine with

and without aura show female preponderance [4] and the

over-representation of women seems more clear-cut in

migraine without aura [3]. In our study all the groups

showed a preponderance of females, including the general population and the two groups of migraine analysed in

our study. Interestingly the female/male RR in patients of

less than 15 years is slightly favourable to the males in the

general population of migraineurs and in migraineurs

without aura. Only the patients with aura showed a female

preponderance in this age group (Table 3). This observation agrees with the previous observations of Bile [15].

They showed that the prevalence of migraine rises from

1% at 6 years of age to 5% at 15 years of age. No sex difference was apparent until age 11; above that age a female

preponderance appeared.The most common age of onset of migraine is in the

second and third decade and onset is infrequent after

middle age [16]. The mean age of onset of migraine in

our cohort is in the second decade, in accordance with

the observations in previous studies. Interestingly, theTable 3 Female/male risk ratio in different groups of age and type of migraineFemales, n (%) Males, n (%) RR (95% CI)General populationLess than 15 years 22 (2) 29 (13) 0.7 (0.41.1)

1529 years 202 (22) 74 (33) 2.7 (2.33.1)

3045 years 367 (40) 86 (38) 4.2 (3.44.7)

4559 years 272 (30) 31 (14) 8.7 (7.79.8)

Over 60 years 58 (6) 6 (3) 9.6 (7.312.5)

Overall 921 (100) 226 (100) 4.8 (3.84.3)Migraine without auraLess than 15 years 9 (2) 21 (17) 0.4 (0.20.8)

1529 years 92 (22) 40 (32) 2.3 (1.82.8)

3045 years 171 (41) 45 (36) 3.8 (3.24.4)

4559 years 118 (28) 16 (13) 7.3 (6.18.8)

Over 60 years 29 (7) 2 (2) 14.5 (9.720.8)

Overall 419 (100) 124 (100) 3.3 (3.03.7)Migraine with auraLess than 15 years 13 (3) 8 (7) 1.6 (0.82.7)

1529 years 110 (22) 38 (35) 2.8 (2.33.4)

3045 years 194 (39) 46 (42) 4.2 (3.64.8)

4559 years 151 (31) 14 (13) 10.7 (9.112.6)

Over 60 years 26 (5) 4 (4) 6.5 (4.29.5)

Overall 494 (100) 110 (100) 4.4 (4.14.9)RR, risk ratio132Table 4 Comorbidity of migraine (n=1147)Disease Females, n (%) Males, n (%) p Total, n (%) (n=921) (n=226) (n=1147)Cardiovascular problems (overall) 139 (15) 9 (4) 0.001 147 (13)

Hypertension 113 (12) 7 (3) 0.06 120 (10)

Raynaud phenomenon 5 (1) 0 (0) 0.56 5 (0.4)

Mitral valve prolapse 3 (0.3) 0 (0) 0.19 3 (0.2)

Ischaemic cardiopathy 7 (1) 0 (0) 0.47 7 (0.6)

Other cardiovascular problems 11 (1) 1 (0.4) 0.11 12 (1)

Neurological problems (overall) 62 (7) 10 (4) 0.20 72 (6)

Epilepsy 15 (2) 3 (1) 0.15 18 (2)

BPPV 25 (3) 3 (1) 0.38 28 (2)

Stroke 1 (0.1) 0 (0) 0.16 1 (0.08)

Other neurological problems 21 (2) 4 (2) 0.14 25 (2.1)

Gastrointestinal problems (overall) 214 (23) 19 (8) 0.001 233 (20)

Functional bowel disorders 164 (18) 16 (7) 0.56 180 (16)

Peptic problems 13 (1) 2 (1) 0.57 15 (1)

Others 37 (4) 1 (0.4) 0.17 38 (3)

Psychiatric problems (overall) 283 (31) 40 (18) 0.001 323 (28)

Depression 191 (21) 21 (9) 0.06 212 (18)

Anxiety disorders 64 (7) 10 (4) 0.73 74 (6)

Other psychiatric problems 28 (3) 9 (4) 0.01 37 (3)BPPV, benign paroxysmal positional vertigoTable 5 Comparison between patients with and without auraWithout aura (n=543) With aura (n=604) pAge, meanSD 37.313.8 37.913.3 0.4

Age of onset of migraine, meanSD 20.010.1 18.910.9 0.08

Height, meanSD 158.511.8 150.18.6 0.08

Weight, meanSD 64.014.1 65.413.3 0.33

Body mass index, meanSD 25.24.4 25.44.7 0.07

Females, n (%) 494 (91) 419 (69) 0.20

Headache in the family, n (%) 334 (62) 383 (63) 0.85

Migraine disability (Grade IV), n (%) 269 (50) 331 (55) 0.17

Nausea, n (%) 451 (83) 542 (90) 0.01

Vomiting, n (%) 285 (52) 412 (68) 0.00

Phonophobia, n (%) 270 (50) 392 (65) 0.00

Photophobia, n (%) 237 (44) 351 (58) 0.00

Cardiovascular problems, n (%) 67 (12) 78 (13) 0.92

Neurological problems, n (%) 29 (5) 43 (7) 0.27

Gastrointestinal problems, n (%) 101 (19) 131 (22) 0.26

Psychiatric problems, n (%) 141 (26) 177 (29) 0.29

Food, n (%) 35 (6) 66 (11) 0.01

Menstruation, n (%) 181 (33) 238 (39) 0.06

Stress, n (%) 52 (10) 55 (9) 0.76age of onset was earlier in males (Table 1). Other

observations such as the larger height and weight of the

Mexican males with migraine are expected observations according to previous studies in the Mexican population [17].MA is a primary headache disorder that affects about

30% of migraine sufferers. In some patients MA is associated with attacks of migraine without aura and this coexistence has sparked a debate as to whether these forms of

migraine are actually clinically distinct entities [18]. The133IHS diagnostic criteria provide a clinical description of

the aura; aura consists of transient, unilateral or bilateral

visual, sensory or motor symptoms considered to arise

from a recurrent reversible, idiopathic dysfunction of the

cortex or brainstem. One of the most important findings in

our study was the high frequency of MA. In the majority

of studies performed in the general population the frequency varies from 15% to 30%. We consider that this

finding could be explained by a reference bias. Both institutions are national reference centres for complex neurological conditions and this could be the reason for the high

prevalence of MA. On the other hand it is worth noting the

high frequency of accompanying symptoms in patients

with aura; this observation could be explained in the same

way as the high frequency of patients with aura. It is possible that the most complicated patients are referred to

specialised centres in Mexico. This preponderance of

patients with MA with more complications and more

symptoms has been seen in studies of epilepsy clinics and

tertiary centres in other populations [19, 20].Migraine and epilepsy are comorbid. Andermann

reported a median epilepsy prevalence of 5.9% (range

1%17%) in migraineurs, which greatly exceeds the population prevalence of 0.5% [21, 22]. Perhaps an altered

brain state increases the risk of both migraine and epilepsy and thus accounts for the comorbidity of these disorders [22]. Genetic or environmental risk factors may

increase neuronal excitability or decrease the threshold for

both types of attacks. A reduction in brain magnesium [23]

or alterations in neurotransmitters provide plausible

potential substrates for this increase in neuronal excitability [24]. In our study the frequency was 2%, which is in

the range of reported frequencies.The comorbidity of migraine with psychiatric conditions is well established [25]. As for affective disorders,

the lifetime prevalence of major depression is 34.4% in

patients with migraine and 10.4% in patients without

migraine. The lifetime prevalence of anxiety disorders in

migraine is significantly increased in comparison to controls with panic disorders (10.9% vs. 1.8%), generalised

anxiety disorders (8.6% vs. 1.8%) and phobic disorders(39.8% vs. 20.6%). In our study the most frequent disorders were depression and anxiety disorders. The main bias

in this observation is the source of the information. As we

comment in methods, we obtained the information from

the clinical charts and a general interview with the

patients. It is possible that if we had done a direct evaluation of psychiatric comorbidity we would have obtained a

higher frequency of these alterations. For this reason the

frequency of depression is lower in our population than

that reported in the literature.The ascertainment of chronic conditions varies in the

different studies performed in several countries. In our

study we used the information contained in charts and the

information supplied by the patient; this being the main

weakness of our study because we could over- or underestimate the prevalence of the different medical conditions. Even so, many researchers have found a good correlation between the different methods of measuring

comorbidity and our method is a widely accepted methodology to ascertain many chronic medical conditions

including hypertension, coronary heart disease, cancer,

arthritis and other cardiovascular diseases. On the other

hand the lack of a control group does not permit the estimation of the prevalence of these chronic medical conditions in the general population to perform a comparison

with migraineurs [10, 26, 27].Many environmental factors and physiologic influences may provoke a migraine attack or increase its severity. Menstruation is a common migraine trigger or

enhancer. Changes in body rhythm such as sleep deprivation, too much sleep or fasting may provoke an attack.

Minor head trauma and changes in weather may trigger

migraine. In approximately 15%20% of patients with

migraine, foods may be a provocative factor; foods that

are related to migraine are chocolate, strong cheeses, citrus fruits and sometimes the sweetener aspartame; they

may all trigger a migraine attack. Excessive use of caffeine-containing foods and caffeine withdrawal may trigger both migraine and tension headaches [28]. In our

study the main trigger was stress in 36%, followed by

menstruation and food, which are classically described as

the principal triggers.In this study we described the clinical characteristics

of a large sample of patients with migraine in Mexico

City. The majority of characteristics of our sample are

similar to other reports, except that in our sample the frequency of MA was higher. This finding could be explained

by a reference bias of the participating institutions, but it

could be explained by genetic and race variations.Acknowledgements We are indebted to Rosalva Badager for providing invaluable insight in the coordination of the study. Other

participants in the study were as follows. Research administration

and data-base personnel: Concepcin Romero and Marcela

Vzquez; Nurse Personnel Ruth Silvestre Rodrguez and Neydi

Madariaga Caldern. We wish to thank FUNSALUD and CONACYT (SNI) which funded J.F.T-Zs postdoctoral fellowship. This

work was supported by a grant from Perlegen Sciences.Group of the Genetic Study of Migraine in Mexico: Bruno Estaol,

Alberto Mimenza-Alvarado, Claudia Domnguez-Fonseca, Carlos

Cant-Brito, Felipe Vega-Boada, Alejandro Orozco-Narvez,

Arturo Domnguez Paz, Luis Villa-Gutirrez, Ruth Silvestre

Rodrguez, Neydi Madariaga-Caldern, Maria Teresa Reyes, Sofa

Snchez, Natasha Alcocer, Sara Aguilar Navarro, Juan C. Muiz-

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