Sage Journals: Discover world-class research

Abstract

Background: Endothelial dysfunction could be involved in the pathophysiology of migraine. The results obtained from a few studies on endothelial dysfunction in migraine are controversial. We investigated brachial flow-mediated dilatation (FMD), which reflects systemic endothelial dysfunction, in migraine patients without comorbidities. By employing strict inclusion criteria we avoided the possible changes to FMD from confounding factors.

Methods. Forty migraine patients without comorbidities (20 with and 20 without aura) and 20 healthy subjects were included. FMD of brachial arteries and carotid intima-media thickness were measured by using standard procedures.

Results. We did not find any difference in FMD between migraine patients and healthy subjects (p = .96). Also, no differences were found among healthy subjects, migraine patients with aura and without aura (p = .99).

Conclusion. Our study showed that systemic endothelial function is not impaired in migraine patients without comorbidities, neither in those with or without aura. Considering these findings, the investigation of cerebral endothelial function would be useful in a further investigation of the role of endothelial (dys)function in migraine pathophysiology.

Keywords

Migraine endothelium flow-mediated vasodilatation

Introduction

Migraine has long been defined as a neurovascular disorder without long-term consequences to the brain or possibly other organs. However, in recent years several studies have associated migraine with cerebrovascular disorders (1–5). The increased prevalence of white matter lesions on MRI and several cases of ischemic strokes during and between migraine attacks indicated an association between migraine and ischemic strokes (6–12). Therefore, migraine has come to be a known “risk factor” for brain ischemia. Furthermore, epidemiological studies suggest that migraine is associated not only with disorders of the cerebral but also coronary, retinal, dermal and peripheral vasculature (13). Some studies have also shown a procoagulatory and proinflammatory state in migraine patients (13). All of these findings suggest a role of endothelial dysfunction in migraine. It is speculated that endothelial dysfunction could lead to migraine or vice versa, migraine could lead to endothelial dysfunction (14–20). Also, it is proposed that migraine may be a local manifestation of systemic vascular abnormality (21,22).

Studies on endothelial function in migraine patients are rare, and they have shown conflicting results. For these purposes flow-mediated dilatation (FMD), a well-known functional method that reflects the endothelial function of systemic arteries through relative change of the brachial artery diameter after ischemia, was used (23,24). Some authors have described decreased FMD in migraine patients (14,21,22,25); others have not found any difference in systemic endothelial function compared to the healthy subjects (26). But none of them employed strict inclusion criteria such as carotid intima-media thickness (IMT) to avoid the possible changes to FMD from confounding factors. Thus, the existence of endothelial dysfunction in migraine patients has yet to be shown.

The aim of our study was to assess systemic endothelial function with FMD in migraine patients without comorbidities during an interictal period by employing strict inclusion criteria and comparing it with that of healthy subjects.

Methods

Forty subjects who fulfilled the diagnostic criteria of migraine (20 with aura and 20 without aura) participated in our study. All migraine patients were diagnosed according to the International Headache Society criteria (second edition) (27). The control group consisted of 20 healthy subjects who had normal somatic and neurological status and did not receive any pharmacological or other kind of therapy. Also, the migraine patients had normal somatic and neurological status. The three groups were matched by gender and age (Table 1). Subjects in the control group were randomly recruited from the hospital staff and acquaintances; none of the subjects in the control group was suffering from headache when the study was conducted and nobody had migraine or other kind of headache. Migraine patients had experienced the last migraine episode more than 24 hours before the investigation.

Table 1.

Biochemical and morphological parameters of healthy subjects, MwA and MwoA

Parameter	Healthy	MwA	MwoA
Age (years)	35.2 ± 6.8	35.8 ± 8.7	35.8 ± 7.5
Gender (males/females)	4/16	4/16	4/16
Total cholesterol (mmol/L)	4.81 ± 0.65	4.68 ± 0.65	4.52 ± 0.92
HDL cholesterol (mmol/L)	1.65 ± 0.31	1.63 ± 0.31	1.64 ± 0.32
LDL cholesterol (mmol/L)	2.79 ± 0.48	2.68 ± 0.66	2.45 ± 0.77
Triglycerides (mmol/L)	0.81 ± 0.32	0.95 ± 0.35	0.84 ± 0.25
Serum glucose (mmol/L)	5.02 ± 0.42	4.55 ± 0.38	4.74 ± 0.46
SBP (mmHg)	116.8 ± 10.5	114.7 ± 9.2	116.7 ± 13.1
DBP (mmHg)	77.0 ± 5.7	78.3 ± 6.2	77.6 ± 8.2
MAP (mmHg)	67.5 ± 8.4	66.4 ± 4.2	68.5 ± 4.8
BMI (kg/m²)	21.5 ± 2.5	21.7 ± 2.4	22.3 ± 2.7

MwA, migraine with aura; MwoA, migraine without aura; SBP, systolic blood pressure; DBP, diastolic blood pressure; MAP, mean arterial pressure; BMI, body mass index.

For all subjects, the major exclusion criteria were body mass index (BMI)<18 or ≥25 kg/m², history of cardiovascular disease, arterial hypertension (systolic blood pressure >140 mmHg or diastolic blood pressure >90 mmHg), diabetes, hypercholesterolemia (total cholesterol >5.5 mmol/L), pregnancy or lactation and regular use of vasoactive drugs (except triptans or other kinds of transient vasoactive antimigraine drugs). Based on medical history, physical and neurological examination and routine laboratory tests, all subjects were in good health.

The study was approved by the National Medical Ethics Committee of the Republic of Slovenia (and all subjects gave written informed consent before being included).

Color-coded duplex sonography of the carotid and vertebral arteries was performed in all patients. IMT was measured according to the Mannheim Intima-Media Thickness Consensus (28) on both sides 2 cm below the bifurcation on the far wall of the common carotid artery. The distance between the characteristic echoes from the lumen-intima and media-adventitia interfaces was measured. Our final IMT value was based on the mean value of three maximal IMT measurements. Subjects with plaques (focal structures that encroach into the arterial lumen of at least 0.5 mm or 50% of the surrounding IMT value or demonstrate a thickness >1.5 mm) were excluded from the study. Based on this criterion, only one person was excluded.

The study was performed in a quiet room under constant conditions between 7.30 and 10.30 a.m. after a fasting period of at least 10 hours. Before the study, fasting blood samples were drawn for total cholesterol, low-density lipoprotein (LDL), high-density lipoprotein (HDL), triglycerides (TAG) and glucose. FMD of the brachial artery was performed according to the recommendations of Corretti et al. and was studied using a high-resolution ultrasound system with a 10-MHz linear array transducer (Aloka, ProSound α10, Tokyo, Japan) located 2–10 cm above the antecubital fossa (29). The right brachial artery was scanned in the longitudinal section and the end-diastolic mean arterial diameter (EMAD) was measured. This diameter was measured with ultrasonic calipers from the leading edge of the anterior wall to the leading edge of the posterior wall of the brachial artery at the end of the diastole period, incident with the R-wave on the simultaneously recorded electrocardiogram. A hyperemic flow increase was induced by inflation of a blood pressure cuff placed around the forearm to a pressure of 50 mmHg higher than the measured systolic blood pressure for four minutes. Hyperemic diameter was recorded inside one minute after cuff deflation. The final scan was performed four minutes later. FMD was expressed as the percentage change in the artery diameter after reactive hyperemia relative to the baseline scan. Absolute changes in diameters (ADC) were also taken (basal condition and after hyperemia).

In the next step systolic blood pressure (SBP), diastolic blood pressure (DBP) and mean arterial blood pressure (MAP) were measured continuously using noninvasive plethysmography (Colin 7000, Komaki-City, Japan).

The following variables were statistically analyzed by the statistic software SPSS 15.0: FMD, EMAD, ADC and IMT. Before using one-way analysis of variance (ANOVA) test a clearly normal distribution of FMD, EMAD, ADC and IMT was found in all three groups. One-way ANOVA with Bonferoni correction was used to compare the relative responses of FMD, EMAD, ADC and IMT among the groups of healthy subjects, and those who had diagnoses of either migraine with aura (MwA) or migraine without aura (MwoA). An independent t-test was used to compare FMD, EMAD, ADC and IMT between the group of healthy subjects and migraine patients and between MwA and MwoA. We also analyzed the association between FMD and IMT in healthy subjects and all migraine patients.

Results

The median monthly headache attack frequency in migraine patients over the previous year was 2.0 ± 1.1 (MwA 1.7 ± 1.0, MwoA 2.3 ± 1.1). The mean duration of the migraine attacks was 10.9 ± 7.6 years (MwA 11.5 ± 8.1 years, MwoA 10.3 ± 7.3 years).

All subjects had normal values of systolic blood pressure, diastolic blood pressure, mean arterial pressure, total cholesterol, HDL, LDL, triglycerides, glucose and body mass index (Table 1). Furthermore, we did not find any difference in the basal EMAD in the right brachial artery between healthy subjects, migraine patients with MwA and MwoA (Table 2).

We did not find any statistically significant difference in values of IMT between the group of healthy subjects and the group of migraine patients (p = .90; Table 2). In the next step of analysis, one-way ANOVA with Bonferoni correction did not show significant any difference in carotid IMT between the group of healthy subjects, MwA and MwoA (p = .76; Figure 1). Also we did not find any difference in IMT between MwA and MwoA (p = .43; Table 2). In that way we convincingly excluded the possibility of early atherosclerotic process in all groups of tested subjects.

Figure 1.

Comparison of IMT in healthy subjects, migraine patients with aura (MwA) and without aura (MwoA) (p = 0.76).

Table 2.

EMAD (basal, peak), ADC, FMD and IMT in all migraine patients, MwA and MwoA and healthy subjects

					Significance of t-test between groups (p)
	All migraine patients (A)	MwA (B)	MwoA (C)	Healthy subjects (D)	A-D	B-C-D	B-C
EMAD-basal (mm)	3.57 ± 0.57	3.64 ± 0.63	3.49 ± 0.50	3.70 ± 0.58	0.41	0.79	0.41
EMAD-peak (mm)	3.79 ± 0.55	3.87 ± 0.63	3.71 ± 0.46	3.92 ± 0.60	0.41	0.67	0.42
ADC (µm)	222.6 ± 96.5	225.3 ± 88.7	220.0 ± 105.6	221.5 ± 105.1	0.97	0.98	0.87
FMD (%)	6.18 ± 3.10	6.19 ± 3.06	6.17 ± 3.22	6.23 ± 3.01	0.96	0.99	0.99
IMT (mm)	0.41 ± 0.06	0.40 ± 0.05	0.42 ± 0.07	0.41 ± 0.07	0.90	0.76	0.43

MwA = migraine with aura, MwoA = migraine without aura, EMAD = end-diastolic mean arterial diameter, ADC = absolute diameter change, FMD = flow mediated vasodilatation, IMT = intima media thickness.

There were no differences in post-hyperemic EMAD between healthy subjects, migraine patients with MwA and MwoA (Table 2). In addition, we did not find any difference in ADC between healthy subjects and all migraine patients (p = .97; Table 2), the group of healthy subjects, migraine patients with MwA and MwoA (p = .98; Table 2) and the group of migraine patients with MwA and MwoA (p = .87; Table 2).

The most important finding was that we did not find any difference in FMD between healthy subjects and migraine patients (p = .96; Table 2). One-way ANOVA with Bonferoni correction did not show any difference between the group of healthy subjects, migraine patients with MwA and MwoA (p = .99; Figure 2). In addition, we did not find any difference between the group of migraine patients with MwA and MwoA (p = .99; Table 2).

Figure 2.

Comparison of FMD in healthy subjects, migraine patients with aura (MwA) and without aura (MwoA) (p = 0.99).

In the last step, analysis of correlations did not show any significant association between IMT of the common carotid artery and FMD in the group of healthy subjects (p = .145; r²= 0.114; Figure 3), and in all migraine patients (p = .148; r²= 0.054; Figure 4).

Figure 3.

The linear regression analysis of FMD to IMT in healthy subjects (p = 0.145; r² = 0.114).

Figure 4.

The linear regression analysis of FMD to IMT in all migraine patients (p = 0.148; r² = 0.054).

Discussion

The main finding of our study was the absence of any difference in FMD between migraine patients without comorbidities and healthy subjects, or between migraine patients without comorbidities with and without aura.

In comparison to the other studies that evaluated systemic endothelial function in migraine patients, our study strictly excluded all confounding factors. To the best of our knowledge, previous studies did not measure and compare carotid IMT in migraine patients and healthy subjects. It is well known that carotid IMT excludes the possibility of early atherosclerotic process and associated endothelial dysfunction (30–32). In our study we did not obtain any difference in carotid IMT between healthy subjects and migraine patients without comorbidities. As no differences in FMD were noted between healthy subjects and migraine patients without comorbidities during the interictal period, evidently those migraine patients had intact systemic endothelial function.

Our findings of non-altered FMD in migraine patients without comorbidities are in agreement with the results of Silva et al., who also did not find altered FMD during the interictal period in migraine patients (26). They concluded that migraine might not be related to endothelial dysfunction. On the contrary, de Hoon and Vanmolkot showed altered reactivity of the systemic vasculature (14,25). Yetkin et al. also proposed that migraine might be a local manifestation of systemic vascular abnormality (21,22). Association of migraine with ischemic heart disease in both women and men could confirm these speculations, but Schurks et al. made a systematic review and meta-analysis of current evidence and they did not find an association between any migraine type and myocardial infarction (3–5,33). They found only the known association between ischemic stroke and MwA. It is known from previous studies that stroke can occur during and between migraine attacks (1,2). Some studies reported that young women and patients with MwA are more prone to this kind of stroke and that the association is independent of other cardiovascular risk factors (34–37). Nevertheless, the risk of stroke in patients with migraine is not restricted to women. A large-scale epidemiologic study in the United States, the National Health and Nutrition Evaluation Survey (NHANES), reported the risk of stroke to be doubled in patients with migraine, both male and female (38). But there is probably an underestimation of the real extent of brain injury in migraine patients in the general population.

On the basis of our own and previous findings, we can say that there is no strong evidence for impaired FMD in migraine patients. FMD, procoagulatory and proinflammatory states as markers of endothelial activation could reflect endothelial dysfunction (13). However, we did not measure circulation markers of endothelial dysfunction, as we believe that FMD is a more direct reflection of endothelial dysfunction.

On the other hand, we cannot exclude isolated cerebral endothelial dysfunction. Recently, Pretnar-Oblak et al. showed that cerebral and systemic endothelial function may not be closely associated (39). Similarly, Kruit et al. reported an increased prevalence of posterior circulation hyperintensive, ischemic-like lesions in migraine patients (40). They also reported that patients with MwA had a higher prevalence of these lesions compared with MwoA and controls. Again, the prevalence of cardiovascular risk factors was not higher in migraine patients with posterior circulation infarct-like lesions compared with those without lesions. This may be due to low cerebral flow, below an ischemic threshold, during and after migraine attacks (41–45). Subclinical cerebellar dysfunction has been also reported in migraine patients (46,47). A significantly higher prevalence of brain stem hyperintensive lesion was also described in migraine patients compared to controls (48). The precise etiology of these lesions in migraine, and the reasons why migraine patients seem to be more susceptible to these kind of vasculo-ischemic brain changes, remain unknown. There are some studies that compared cerebrovascular reactivity (CVR) to carbon dioxide (CO₂) levels in migraine patients (49–55). Hyper-reactivity, hyporeactivity and no difference in reactivity were observed. However, there are few studies that have specifically compared CVR to CO₂ between both cerebral circulations. Silvestrini et al. have shown that migraine patients with MwA had significantly lower vascular reactivity in the basilar artery (56). These findings suggest that endothelial dysfunction may be primarily located in the arteries of the cerebral circulation, particularly in the territory of the posterior cerebral circulation.

Taking these and our results together, we can conclude that systemic endothelial function is not altered during the interictal period in migraine patients without comorbidities, with and without aura, compared to healthy subjects. In light of these findings, however, the investigation of cerebral endothelial function in migraine patients would be beneficial.

Footnotes

Acknowledgments

The author expresses gratitude to Valentin Beznik and Marjeta Švigelj for technical assistance, and special thanks to all study volunteers.

Funding

This research received no specific grant from any funding agency in the public, commercial or not-for-profit sectors.

Conflicting interests

The author declares no conflict of interest.

References

Tzourio

Iglesias

Hubert

. Migraine and risk of ischaemic stroke: a case control study. BMJ 1993; 307: 289–292.

Buring

Hebert

Romero

. Migraine and subsequent risk of stroke in the physicians’ health study. Arch Neurol 1995; 52: 129–134.

Stang

Carson

Rose

. Headache, cerebrovascular symptoms, and stroke: the Atherosclerosis Risk in Communities Study. Neurology 2005; 64: 1573–1577.

Igarashi

Sakai

Kan

Okada

Tazaki

. Magnetic resonance imaging of the brain in patients with migraine. Cephalalgia 1991; 11: 69–74.

Kruit

van Buchem

Hofman

. Migraine as a risk factor for subclinical brain lesions. JAMA 2004; 291: 427–434.

Henrich

Sandercock

Warlow

Jones

. Stroke and migraine in the Oxfordshire community stroke project. J Neurol 1986; 233: 257–262.

Bogousslavsky

Regli

Van Melle

Payot

Uske

. Migraine stroke. Neurology 1988; 38: 223–227.

Rothrock

Walicke

Swenson

Lyden

Logan

. Migrainous stroke. Arch Neurol 1988; 45: 63–67.

Sacquegna

Andreoli

Baldrati

. Ischaemic stroke in young adults: the relevance of migrainous infarction. Cephalalgia 1989; 9: 255–258.

10.

Rothrock

North

Madden

Lyden

Fleck

Dittrich

. Migraine and migrainous stroke: risk factors and prognosis. Neurology 1993; 43: 2473–2476.

11.

Sochurkova

Moreau

Lemesle

Menassa

Giroud

Dumas

. Migraine history and migraine-induced stroke in the Dijon stroke registry. Neuroepidemiology 1999; 18: 85–91.

12.

Swartz

Kern

. Migraine is associated with magnetic resonance imaging white matter abnormalities: a meta-analysis. Arch Neurol 2004; 61: 1366–1368.

13.

Tietjen

. Migraine as a systemic vasculopathy. Cephalalgia 2009; 29: 987–996.

14.

Vanmolkot

van Bortel

de Hoon

. Altered arterial function in migraine of recent onset. Neurology 2007; 68: 1563–1570.

15.

Ciancarelli

Tozzi-Ciancarelli

Di Massimo

Marini

Carolei

. Urinary nitric oxide metabolites and lipid peroxidation by-products in migraine. Cephalalgia 2003; 23: 39–42.

16.

Cesar

Garcia-Avello

Vecino

Sastre

Alvarez-Cermeno

. Increased levels of plasma von Willebrand factor in migraine crisis. Acta Neurol Scand 1995; 91: 412–413.

17.

Gallai

Sarchielli

Firenze

. Endothelin 1 in migraine and tension-type headache. Acta Neurol Scand 1994; 89: 47–55.

18.

Sarchielli

Alberti

Baldi

. Proinflammatory cytokines, adhesion molecules, and lymphocyte integrin expression in the internal jugular blood of migraine patients without aura assessed ictally. Headache 2006; 46: 200–207.

19.

Leira

Sobrino

Rodriguez-Yanez

Blanco

Arias

Castillo

. Mmp-9 immunoreactivity in acute migraine. Headache 2007; 47: 698–702.

20.

Tzourio

El Amrani

Poirier

Nicaud

Bousser

Alperovitch

. Association between migraine and endothelin type A receptor (ETA -231 A/G) gene polymorphism. Neurology 2001; 56: 1273–1277.

21.

Yetkin

Ozisik

Ozcan

Aksoy

Turhan

. Decreased endothelium-dependent vasodilatation in patients with migraine: a new aspect to vascular pathophysiology of migraine. Coron Artery Dis 2006; 17: 29–33.

22.

Yetkin

Ozisik

Ozcan

Aksoy

Turhan

. Increased dilator response to nitrate and decreased flow-mediated dilatation in migraineurs. Headache 2007; 47: 104–110.

23.

Raitakari

Celermajer

. Flow-mediated dilatation. Br J Clin Pharmacol 2000; 50: 397–404.

24.

Celermajer

Sorensen

Gooch

. Non-invasive detection of endothelial dysfunction in children and adults at risk of atherosclerosis. Lancet 1992; 340: 1111–1115.

25.

de Hoon

Willigers

Troost

Struijker-Boudier

van Bortel

. Cranial and peripheral interictal vascular changes in migraine patients. Cephalalgia 2003; 23: 96–104.

26.

Silva

Rueda-Clausen

Silva

. Endothelial function in patients with migraine during the interictal period. Headache 2007; 47: 45–51.

27.

Headache Classification Subcommittee of the International Headache Society. The International Classification of Headache Disorders, 2nd edition. Cephalalgia 2004; 24 Suppl 1: 9–160.

28.

Touboul PJ, Hennerici MG, Meairs S, et al (Advisory Board of the 3rd Watching the Risk Symposium, 13th European Stroke Conference.) Mannheim intima-media thickness consensus. Cerebrovasc Dis 2004;18:346–349.

29.

Corretti

Anderson

Benjamin

. Guidelines for the ultrasound assessment of endothelial-dependent flow-mediated vasodilation of the brachial artery. A report of the International Brachial Artery Reactivity Task Force. J Am Coll Cardiol 2002; 39: 257–265.

30.

Zureik

Ducimetiere

Touboul

. Common carotid intima-media thickness predicts occurrence of carotid atherosclerotic plaques: longitudinal results from the Aging Vascular Study (EVA) study. Arterioscler Thromb Vasc Biol 2000; 20: 1622–1629.

31.

Davis

Dawson

Riley

Lauer

. Carotid intimal-medial thickness is related to cardiovascular risk factors measured from childhood through middle age: the Muscatine study. Circulation 2001; 104: 2815–2819.

32.

Simon

Gariepy

Chironi

Megnien

Levenson

. Intima-media thickness: a new tool for diagnosis and treatment of cardiovascular risk. J Hypertens 2002; 20: 159–169.

33.

Schürks

Rist

Bigal

Buring

Lipton

Kurth

. Migraine and cardiovascular disease: systematic review and meta-analysis. BMJ 2009; 339: b3914–b3914.

34.

Bousser

Welch

. Relation between migraine and stroke. Lancet Neurol 2005; 4: 533–542.

35.

Kruit

Launer

Ferrari

van Buchem

. Infarcts in the posterior circulation territory in migraine. The population-based MRI CAMERA study. Brain 2005; 128: 2068–2077.

36.

Tzourio

Tehindrazanarivelo

Iglesias

. Case-control study of migraine and risk of ischaemic stroke in young women. BMJ 1995; 310: 830–833.

37.

Kurth

Gaziano

Cook

Logroscino

Diener

Buring

. Migraine and risk of cardiovascular disease in women. JAMA 2006; 296: 283–291.

38.

Merikangas

Fenton

Cheng

Stolar

Risch

. Association between migraine and stroke in a large-scale epidemiological study of the United States. Arch Neurol 1997; 54: 362–368.

39.

Pretnar-Oblak

Šabovič

Zaletel

. Associations between systemic and cerebral endothelial impairment determined by cerebrovascular reactivity to L-arginine. Endothelium 2007; 14: 1–8.

40.

Kruit

Launer

Ferrari

van Buchem

. Infarcts in the posterior circulation territory in migraine. The population-based MRI CAMERA study. Brain 2005; 128: 2068–2077.

41.

Woods

Iacoboni

Mazziotta

. Brief report: bilateral spreading cerebral hypoperfusion during spontaneous migraine headache. N Engl J Med 1994; 331: 1689–1692.

42.

Olesen

Friberg

Olsen

. Timing and topography of cerebral blood flow, aura, and headache during migraine attacks. Ann Neurol 1990; 28: 791–798.

43.

Bednarczyk

Remler

Weikart

Nelson

Reed

. Global cerebral blood flow, blood volume, and oxygen metabolism in patients with migraine headache. Neurology 1998; 50: 1736–1740.

44.

Cutrer

Sorensen

Weisskoff

. Perfusion-weighted imaging defects during spontaneous migrainous aura. Ann Neurol 1998; 43: 25–31.

45.

Sanchez del Rio

Bakker

. Perfusion weighted imaging during migraine: spontaneous visual aura and headache. Cephalalgia 1999; 19: 701–707.

46.

Sandor

Mascia

Seidel

De Pasqua

Schoenen

. Subclinical cerebellar impairment in the common types of migraine: a three-dimensional analysis of reaching movements. Ann Neurol 2001; 49: 668–672.

47.

Harno

Hirvonen

Kaunisto

. Subclinical vestibulocerebellar dysfunction in migraine with and without aura. Neurology 2003; 61: 1748–1752.

48.

Kruit

Launer

Ferrari

van Buchem

. Brain stem and cerebellar hyperintense lesions in migraine. Stroke 2006; 37: 1109–1112.

49.

Harer

von Kummer

. Cerebrovascular CO₂ reactivity in migraine: assessment by transcranial Doppler ultrasound. J Neurol 1991; 238(1): 23–26.

50.

Sakai

Meyer

. Abnormal cerebrovascular reactivity in patients with migraine and cluster headache. Headache 1979; 19(5): 257–266.

51.

Thomas

Harpold

Troost

. Cerebrovascular reactivity in migraineurs as measured by transcranial Doppler. Cephalalgia 1990; 10(2): 95–99.

52.

Thomsen

Iversen

Olesen

. Increased cerebrovascular pCO₂ reactivity in migraine with aura -a transcranial Doppler study during hyperventilation. Cephalalgia 1995; 15(3): 211–215.

53.

Valilkovics

Olah

Fülesdi

. Cerebrovascular reactivity measured by transcranial Doppler in migraine. Headache 1996; 36(5): 323–328.

54.

Arjona

Perula de Torres

Serrano-Castro

Guardado-Santervas

Olivares

Rubi-Callejon

. A transcranial Doppler study in interictal migraine and tension-type headache. J Clin Ultrasound 2007; 35(7): 372–375.

55.

Totaro

Marini

De Matteis

Di Napoli

Carolei

. Cerebrovascular reactivity in migraine during headache-free intervals. Cephalalgia 1997; 7: 191–194.

56.

Silvestrini

Baruffaldi

Bartolini

. Basilar and middle cerebral artery reactivity in patients with migraine. Headache 2004; 44(1): 29–34.

Endothelium-dependent vasodilatation in migraine patients

Abstract

Keywords

Introduction

Methods

Results

Discussion

Footnotes

Acknowledgments

Funding

Conflicting interests

References