Y. Yanga*, Z.-N. Guob*, J. Wua*, H. Jina, X. Wangc, J. Xuc, J. Fenga and Y. Xinga

aDepartment of Neurology, The First Norman Bethune Hospital of Jilin University, Chang Chun, China; bCenter for Neurovascular

Ultrasound, The First Norman Bethune Hospital of Jilin University, Chang Chun, China; and cDepartment of Electrodiagnosis, The First

Norman Bethune Hospital of Jilin University, Chang Chun, China

Keywords:

contrast-enhanced

transcranial Doppler,

migraine, right-to-left

shunt

Received 16 March 2012

Accepted 23 May 2012

Background: Recently, contrast-enhanced transcranial Doppler (cTCD) studies have shown that right-to-left shunt (RLS) may be a risk factor for migraine in Westerners; however, limited data in the literature describes the prevalence of RLS in Chinese patients with migraine.

Objective: To assess the prevalence of RLS in patients with migraine in China and to evaluate the relationship between the extent of RLS and migraine.

Methods: A total of 217 consecutive patients with a diagnosis of migraine and 100 volunteers were recruited. cTCD was used to assess the prevalence and the extent of RLS in all subjects.

Results: In the migraine group, the rate of positive RLS was 44.2% (96/217), with 23.5% (51/217) of these being large. In the healthy group, 28.0% (28/100) were positive for RLS overall, and 5.0% (5/100) were large (P = 0.006; P < 0.001). In patients having migraines with aura (MwA), 66.1% (39/59) were positive for RLS overall, and 37.3% (22/59) were large, which was significantly higher when compared with the healthy group (P < 0.001; P < 0.001); in patients having migraines without aura (MwoA), 36.1% (57/158) were positive for RLS overall, and 18.4% (29/158) were large, which was against significantly higher (P < 0.001; P = 0.003). In the MwoA group, the large RLS rate was also higher than in the healthy group (P = 0.002).

Conclusions: A close correlation has been documented between RLS and migraine, especially MwA, but these relationships exist only when the shunts were large.

Introduction

Migraine is a chronic neurological disorder characterized by moderate to severe headaches, and it might have one or all symptoms, including photophobia, throbbing, nausea, and vomiting. It has an estimated prevalence of 8–13% in the Western population, with more than 55 million Europeans and Americans experiencing migraine [1,2]. However, the spectrum of diseases varies in different ethnic groups, and earlier studies have observed that Chinese people have a much lower migraine prevalence (0.987–3.9%) than Westerners [3,4].

Correspondence: Y. Xing, Department of Neurology, The First Norman Bethune Hospital of Jilin University, Jilin University, Xinmin Street 71#, 130021, Changchun, China (tel.: 86 15844047846; fax: 86 431 88782378; e-mail: xingyq@sina.com). *Yi Yang, Zhen-Ni Guo and Jiang Wu contributed equally to the manuscript.

Migraine is a common and complex brain disorder. The underlying pathogenesis is not well understood. Recently, contrast-enhanced transcranial Doppler (cTCD) studies have shown that right-to-left shunt (RLS), usually attributed to a patent foramen ovale (PFO), may be a risk factor for migraine and, in particular, migraine with aura (MwA) [5,6]. Previously published studies found that RLS is quite common in the general population in Western countries, with a prevalence of approximately 10% to 25% depending on the population studied and the methodology used for diagnosis [7]. The aim of this study was to assess the prevalence of RLS in migraine, MwA, migraine without aura (MwoA) patients, and healthy people in China to evaluate the relationship between the extent of RLS and migraine. To the best of our knowledge, this is the first report describing the prevalence of RLS in Chinese patients with migraine.

Methods

Participants

The study design was approved by the Ethics Committee of the First Norman Bethune Hospital of Jilin University. Informed consent was obtained from all subjects. From April 2010 to February 2011, two hundred and seventeen consecutive patients with a diagnosis of migraine (35.03 ± 12.73 years old, 63 males, 154 females) were recruited from the Department of Neurology at the First Norman Bethune Hospital of Jilin University. Patients with Migraine were divided into two groups: MwA (59 cases, 32.15 ± 13.26 years old, 19 males, 40 females) and MwoA (158 cases, 36.11 ± 12.40 years old, 44 males, 114 females). Each patient was diagnosed with migraines by two neurologists according to the International Headache Society Criteria [8]. One hundred healthy volunteers without migraine (medical students, nurses, and doctors in our department) were recruited as normal controls. The average age of the healthy group was slightly younger than the migraine and MwoA groups, but there were no significant differences in gender between the four groups. The average age in the various groups were all within 30–40 years old (Table 1). Subjects with stenotic intracranial or extracranial arteries or intracranial abnormalities diagnosed with transcranial Doppler (TCD; EMS-9, Delica, China), carotid ultrasound (IU22; Phillips, Andover, MA, USA), or magnetic resonance imaging (1.5T-MRI, GE, Waukesha, WI, USA) were excluded. The clinical workup consisted of a thorough physical examination, laboratory tests including liver and kidney function tests, hematology profiles, TCD, carotid ultrasound, cTCD (MultiDop 94; DWL, Sipplinghen, Germany), and MRI.

cTCD protocol

An 18-gauge needle was inserted into the cubital vein in the supine position. Insonation of one middle cerebral artery (MCA) using TCD was performed. Contrast agent was prepared using 9 ml isotonic saline solution, 1 ml air, and a drop of the patient’s blood that was vigorously mixed between two 10-ml syringes via a 3-way stopcock [9–11]. After 30 mixing cycles, the contrast agent was injected as a rapid bolus [9]. The first injection was performed during normal respiration (rest), and the second injection was performed 5 s prior to the start of a ten-second valsalva maneuver (VM). The strength of the VM was measured by peak flow velocity along the Doppler curve. The time when the first microbubble (MB) appears at the MCA level was noted [9,10]. The maximum number of bubbles recorded from the MCA in each case either during normal breathing or after VM was taken as the estimate of the maximum degree of shunt [12]. Two ultrasound technologists and one neurologist, each blinded to the diagnosis of migraine, were designated to assess the prevalence and extent of RLS in all subjects. On the basis of the standards reported by Jauss and Serena, a four-level RLS categorization based on the MB count was applied as follows: none, 0 MBs (negative result, Fig. 1a); mild, 1–10 MBs (Fig. 1b); moderate, 10 < MBs  25 (Fig. 1c); and large, >25 MBs (Fig. 1d) [9,10]. RLS was considered latent if it occurred only after VM and permanent when it occurred also at rest. RLS was considered to be small if mild or moderate RLS was detected [9,13,14].

Statistics

The statistical program for social sciences version 12.0 (SPSS; IBM, West Grove, PA, USA) was used to analyze all the data. Differences between groups were analyzed with the t-test for continuous variables and the chisquared test for nominal variables. All tests were twotailed, and the level of significance was set at P < 0.05.

Results

In the migraine group, 44.2% (96 of 217) had a positive RLS result, 53 of 96 cases were permanent (55.2%) and 43 cases were latent (44.8%). In the MwA group, 66.1% (39 of 59) had a positive RLS result, 22 cases were permanent (56.4%) and 17 cases were latent (43.6%). In the MwoA group, 36.1% (57 of 158) had a positive result, 31 cases were permanent (54.4%) and 26 cases were latent (45.6%). In the healthy group, 28.0% (28 of 100) had a positive RLS result, 17 cases were permanent (60.7%) and 11 cases were latent (39.3%). There were no significant differences in permanent and latent in the various groups (Table 2). In the following text, we analyzed the relationship between maximum degree of shunt and migraine (MwA and MwoA) in the various groups.

Delica--Prevalence and extent of right-to-left shunt in migraine a survey.pdf