10 Headache Medicine, v.2, n.1, p. 10-12, jan./feb./mar. 2011

Cerebrovascular reactivity in migraineurs

Vasorreatividade cerebral em migranosos

ABSTRACTABSTRACT

ABSTRACT

Cerebrovascular reactivity (CR) assessed by transcranial

Doppler (TCD) has been evaluated among migraineurs with

conflicting results. We assessed the CR using the breath holding

index (BHI) among 228 migraineurs during ictal or interictal

phase and 56 controls. Migraineurs exhibited increased BHI

values in the interictal phase and reduced BHI in the ictal

phase when compared to controls.

eywords:eywords:

eywords: Transcranial Doppler Ultrasonography; Migraine

disorders; Headache; Cerebrovascular circulation.

RESUMORESUMO

RESUMO

A vasorreatividade cerebral medida pelo Doppler transcra-

niano tem sido avaliada em pacientes com migrânea com

resultados conflitantes. Nós avaliamos a vasorreatividade

cerebral utilizando o índice de apnéia (IA) em 228 pacientes

com o diagnóstico de migrânea nas fases ictal e interictal e

56 controles. Os pacientes apresentaram valores do IA

aumentados durante a fase interrictal e reduzidos durante a

fase ictal quando comparados aos controles.

Descritores:Descritores:

Descritores: Ultrassonografia Doppler transcraniana;

Migrânea; Cefaleia; Circulação cerebrovascular

ORIGINAL ARTICLEORIGINAL ARTICLE

ORIGINAL ARTICLE

Arthur de Carvalho Jatobá e Sousa

, Ciro Martins Gomes

, Rodolfo de Souza Coelho

, Ricardo Afonso Teixeira

Instituto do Cérebro de Brasília, Brasília, DF, Brazil;

Hospital Universitário de Brasília, Brasília, DF, Brazil

Hospital de Base do Distrito Federal, Brasília, DF, Brazil

Sousa AC, Gomes CM, Coelho RS, Teixeira RA

Cerebrovascular reactivity in migraineurs. Headache Medicine. 2011;2(1):10-12

neuronal and/or vascular dysfunction,

(1)

which may be

due to genetic mutations associated to ion-transporting

mechanisms.

(2)

Conflicting results about cerebrovascular reactivity

and cerebral blood flow velocities have been described

among migraineurs. A few studies have reported an

increased cerebrovascular reactivity (CR),

(3,4)

while others

a normal and even a reduced CR.

(5-8)

The diagnosis of migraine headaches can be usually

made on clinical grounds alone in most patients. However,

it would be interesting to find a complementary assessment

tool to support its diagnosis. Cerebrovascular reactivity

assessed by transcranial Doppler could be a noninvasive

and cost effective tool that could possibly help in the

differential diagnosis of primary headaches.

The aim of this study is to compare the CR among

patients with migraine and controls. Our hypothesis is that

migraineurs show different CR status when compared to

controls.

METHODS

Two hundred and twenty eight consecutive migraineurs

were included in the study under informed consent

conditions (mean age = 33.82 years; range = 13 - 67;

women= 189). One hundred and fifty nine patients were

evaluated in the interictal period: 71 suffering from

migraine with aura (MA) and 88 from migraine without

aura (MWA). In addition, we evaluated 69 patients during

headache attacks: 36 with MA, 33 with MWA. We

compared the results to a control group of 56 individuals

INTRODUCTION

Migraine is one of the most common types of primary

headaches in clinical practice, but its pathophysiology is

not completely elucidated. The mechanism of migraine

headaches appears to involve the activation of the

trigeminocervical pain system by stimuli elicited by

Headache Medicine, v.2, n.1, p. 10-12, jan./feb./mar. 2011 11

with no personal history of headache (mean age = 42.41

years; range = 15-75; 31 women). All patients were

recruited from the neurology clinic of Santa Luzia Hospi-

tal in the city of Brasília - Brazil, from February 2003 to

June 2005. None of the patients was using prophylactic

antimigraine medication. Neither patients nor controls had

any antecedent of major disease and no vascular risk

factors such as hypertension, diabetes, dyslipidemia,

smoking. Diagnosis of migraine was made according

to the 1988 international classification of headache

disorders - 1 (ICHD-I).

(9)

In 2004 a revised international

classification of headache disorders (ICHD-II) was

published.

(10)

Since we had already started recruiting

patients using the ICHD-1, we carried on our study using

this previous classification. The study was conducted with

full approval by the institutional review boards.

The transcranial Doppler (TCD) study was carried

out in a quiet room with the individuals in supine position,

always during the afternoon. The reactivity to hypercapnia

was measured by the breath holding index (BHI). The

index was obtained by dividing the percentage increase

in mean flow velocity occurring during breath-holding by

the time (30 seconds) subjects held their breath after a

period of three minutes of normal breathing. We

considered the peak maximum value of the velocity curve,

which usually occurs a few seconds after the release. This

method has been validated as effective as methods

requiring carbon dioxide inhalation or acetazolamide

administration. We used an EZ-Dop transcranial Doppler

instrument (DWL Elektronische Systeme GmbH), with a

2-MHZ transducer fitted on a headband. The mean of

right and left BHI values were calculated.

ANOVA test and Tukey post hoc pairwise comparisons

were applied for comparisons on continuous variables

among the groups. The level of significance was set at

0.05.

RESULTS

All patients were able to hold their breath during 30

seconds when submitted to the test. Mean values of BHI

for migraineurs and controls are given in Table 1.

We found an increased BHI among migraineurs in

the interictal phase when compared to the control group

(migraine-interictal = 1.35; range = 0.37-2.87; controls

= 1.04; range = 0.535-1.177; p-value<0.001). During

migraine attacks, a significant decrease in BHI was

observed when compared to controls (migraineurs-ictal

= 0.82; range = 0.18-1.505; controls = 1.04; range

= 0.535-1.177; p-value < 0.001).

The BHI mean values were similar when comparing

migraineurs with aura and without aura in the ictal phase

(MA-ictal = 0.87; range = 0.18-1.41; MWA-ictal = 0.78;

range = 0.305-1.505; p = 0.214) and interictal phase

(MA-interictal = 1.35; range = 0.37-2.87; MWA-interictal

= 1.36; range = 0.465-2.305; p-value = 0.778).

DISCUSSION

Headache is a usual patient complaint in almost every

medical specialty. The very common occurrence of this

symptom in our population can lead to an expressive

economic loss and can also limit patients in ordinary life

activities. In the United States migraine affects about 12%

of the population, being three times more prevalent in

women than men, negatively affecting daily functioning

of most patients.

(11)

In Brazil, the prevalence of migraine

is estimated to be about 15%, being 2.2 times more

prevalent in women.

(12)

The use of the ICHD criteria for migraine headaches

can be considered a reliable tool to its diagnosis in most

patients. A large population-based study showed that self-

reported migraine among women was confirmed in 87%

when applying the ICHD-II criteria for migraine or

probable migraine without aura.

(13)

Although most patients

can be diagnosed on clinical grounds using the ICHD-II

criteria, sometimes the correct diagnosis of migraine

represents a challenge for both clinical practice and clinical

research.

The transcranial Doppler has been evaluated by some

studies as a potential tool for this purpose. Studies that

measured CR in the interictal phase have yielded conflicting

results, which may be due to different study methodologies.

Silvestrini et al. reported similar BHI in controls and in

patients during headache free periods. In this study the

BHI was calculated using the mean cerebral blood flow

(CBF) 4 seconds after the release.

(14)

Another study found

an exaggerated interictal BHI in migraineurs without aura

compared with the control group.

(4)

This study considered

the maximum point of CBF to calculate CR, which was

the methodology used in our study.

CEREBROVASCULAR REACTIVITY IN MIGRAINEURS

12 Headache Medicine, v.2, n.1, p. 10-12, jan./feb./mar. 2011

Correspondence

DrDr

. Ricardo A. Ricardo A

. Ricardo A

. T. T

. T

eixeiraeixeira

eixeira

Instituto do Cérebro de Brasília

SHLS 716 - Conjunto L - Centro Clínico Sul - Torre II

andar - Sala 211

70390-700 – Brasília, DF, Brazil

Tel. (61) 3346-5383 - Fax. (61) 3346-9102

ricardoateixeira@yahoo.com

Studies that used different stimuli (e.g.; CO2

inhalation, hyperventilation) reported normal

(5,6)

reduced

(7,8)

CR in the interictal period. Other studies using

methods such as Xenon blood flow studies, SPECT, PET,

and functional magnetic resonance also reported

discordant results. The different methods of CR

measurement is a major factor that limits comparison

between studies.

Migraineurs might have an increased CR during the

headache-free period due to alterations in their autonomic

tonus. These patients might have a state of vagal

hyperactivity during headache free periods leading to an

enhanced vasodilatatory response. Furthermore, it has been

reported that migraineurs present an enhanced secretion

and response to nitric oxid.

(15)

A previous comparison between tension-type

headache (TTH) and migraine using the transcranial

Doppler was performed by Rosengarten et al., measuring

the evoked flow velocity in the posterior cerebral artery

utilizing a visual stimulation paradigm.

(16)

This study

showed that TTH patients had similar flow velocity

response during the ictal and interictal periods, which

was also comparable to controls. The same evaluation

in migraineurs demonstrated that CR was reduced during

the ictal phase when compared to the interictal phase,

suggesting an impaired vasodilatation reserve during the

ictal phase.

Our study has several limitations. Individuals evaluated

in the ictal phase were not the same ones tested in the

interictal phase. We did not control for the presence of

carotid stenosis, which can influence the breath holding

index. However, the mean age of the migraineurs and

the control group was relatively low to be influenced by

this variable.

In addition, due to the wide BHI variability found

among migraineurs, it does not seem possible to set a

BHI cutoff value to define migraine using the transcranial-

Doppler. However, it is tempting to consider that a

significant CR variation between ictal and interictal phase

in a single patient could be an additional information to

the diagnosis of migraine. Further research evaluating CR

of the same patient during ictal and interictal phases of

migraine would be of great value.

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SOUSA AC, GOMES CM, COELHO RS, TEIXEIRA RA