Wei Du,1 XiujuanWu,1 Yingqi Xing,1 Yunlong Geng,2 Jing Bai,1 and Xiaonan Song1 1Neuroscience Center, Department of Neurology,The First Hospital of Jilin University, Jilin University, Changchun 130021, China
2Department of Clinical Medicine, Jilin University, Changchun, Jilin 130021, China Correspondence should be addressed to Jing Bai; baijing0304@163.com and Xiaonan Song; songxiaonan2009@sina.com
Received 21 May 2015; Accepted 23 June 2015
Academic Editor: Alessandro Giardini
Copyright ? 2015 Wei Du et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Right-to-left shunt (RLS) is associated with cryptogenic stroke and migraine. Herein we investigated the relationship between RLS and silent lacunar infarcts in patients with migraine. A total of 263 patients with migraine who met eligibility criteria were enrolled from January 2010 to December 2011, among which 127 subjects fell into RLS group. Baseline demographics were comparable between RLS and non-RLS groups (?? > 0.05). The incidence of silent lacunar infarcts in RLS group was not significantly different from that of the non-RLS group (25.2% versus 21.3%, ?? > 0.05). Furthermore, we found that the incidence of silent lacunar infarcts in permanent and latent RLS subgroups was comparable with non-shunt RLS subgroup (28.6% versus 24% versus 21.3%, ?? > 0.05). Similarly, the incidence of silent lacunar infarcts in the non-RLS group, mild-shunt group, and large-shunt group was also comparable (21.3% versus 23.8% versus 29.3%, ?? > 0.05). In addition, RLS did not increase the incidence of silent lacunar infarcts in migraine patients with elder age (<50 years age group: 15.8% versus 17.9%; ≥50 years age group: 53.1% versus 37.5%, both ?? > 0.05). In conclusion, RLS does not increase the incidence of silent lacunar infarcts in patients with migraine. Further prospective studies are warranted to validate this finding.
1. Introduction
Silent lacunar infarcts can eventually cause cognitive dysfunction, dementia, and depression [1]. Additionally, patients who have these infarcts have been reported to have a significantly increased risk of symptomatic stroke, which reduces the patient’s quality of life and ability to work [2]. With improvements in medical technology and the accuracy of diagnostic instruments, silent lacunar infarcts can now be more precisely diagnosed; however, their etiology and pathogenesis remain unclear. In recent years, studies have focused onwhether the rightto- left shunt (RLS) leads to an increased risk of stroke and the conclusions have been controversial. To our knowledge, the most common cause of RLS is a patent foramen ovale (PFO), which was not previously thought to cause or trigger reversed blood flow affecting the hemodynamics of the heart. However, recent studies have shown that PFO is related to unexplained cerebral infarction, migraine, decompression sickness, systemic arterial embolism, and sleep apnea. Several studies have shown that a significant statistical relationship exists between RLS and migraine [3–5]. In addition, RLS is widely recognized as causing a “paradoxical embolism” type stroke, which refers to emboli from the venous system and/or right atrium flowing into the systemic circulation, leading to ischemic stroke and embolism of the heart, kidney, and peripheral arteries. Controversy exists over the mechanism of paradoxical embolism, but a potential direct relationship has been established between stroke and PFO. In a previous study [6], symptomatic stroke with acute infarcts revealed by magnetic resonance imaging (MRI) scans was found to be associated with PFO. However, few studies have focused on whether silent lacunar infarcts in patients with migraine correlate with RLS. In this study, we investigated the relationship between RLS and silent lacunar infarcts; that is, whether RLS could increase the prevalence of silent lacunar infarcts in patients with migraine. We also explored the relationship between different types of RLS, detected by the transcranial Doppler (TCD) bubble test, and the prevalence of silent lacunar infarcts, revealed by MRI of the head.
2. Subjects and Methods
2.1. Subjects. The studywas approved by the ethics committee of The First Hospital of Jilin University, Changchun, China. Written informed consentwas obtained from all the recruited patients. From January 2010 to December 2011, patients with migraine who visited the neurology clinic at The First Hospital of Jilin University and simultaneously met our inclusion and exclusion criteria were enrolled in the study. The inclusion criteria were as follows: (1) patients had a history of migraine for at least 1 year, and the diagnosis of migraine met with the diagnostic criteria for migraine revised by the Head and Face Pain Classification Committee of the International Headache Society [7]; (2) patients had no symptoms of transient ischemic attack (TIA) or ischemic stroke and had signed the consent forms. The exclusion criteria were as follows: (1) patients who refused to undergo a head MRI or the TCD bubble test and (2) those with intracranial or extracranial artery stenosis demonstrated by TCD and carotid ultrasound, or with other central nervous system diseases such as multiple sclerosis, cerebral hemorrhage, cerebral vascular malformations, and brain tumors.All the patients enrolled underwent conventional TCD (EMS-9, Delica, China), carotid ultrasound (IU22, Phillips, Andover, MA), head MRI, and TCD bubble test. In addition, the common risk factors for ischemic stroke in these patients, including hypertension, diabetes, coronary heart disease, hyperlipidemia, and history of smoking, were recorded.
2.2. TCD Bubble Test. A German DWL Multi-DopX4 transcranial Doppler was used in the TCD bubble test.The head fixed probe was applied, the probe frequency was 2MHz, and the unilateral middle cerebral artery was monitored.The monitoring depth was 40–60 mm, and the ?? membrane and blood velocity curve were simultaneously indicated. Specifically trained TCD doctors recorded all parameters. Before the test, patients were asked to practice a standardized Valsalva maneuver. An 18-gauge needle was inserted into the cubital vein in the supine position. Contrast agent was prepared using 9mL isotonic saline solution, 1mL air, and a drop of the patient’s blood that was vigorouslymixed between two 10mL syringes via a 3-way stopcock. After 30 mixing cycles, the contrast agent was injected as a rapid bolus. The first injectionwas performed during normal respiration (rest) and the second injection was performed 5 s prior to the start of a 10 s Valsalva maneuver. The time interval between injections was 2min. The strength of the Valsalva maneuver wasmeasured by peak flow velocity along the Doppler curve. The time at which the first microbubble appeared at the middle cerebral artery (MCA) level was noted.Themaximum number of microbubble count (MBs) scored in the MCA for each patient, either during normal breathing or after the Valsalva maneuver, was taken as the estimate of the maximum degree of shunt. Based on the MBs detected by the TCD bubble test, the degree of shunt in patients with RLS was identified and patients were subsequently divided into the mild-shunt group (1–10MBs) and large-shunt group (>10MBs), while patients without RLS fell into the non-RLS group, that is, nonshunt group [8]. In addition, the type of RLS could be divided into permanent and latent RLS, depending on when the MBs were detected. Permanent RLS was defined when MBs were detected both at baseline and after the Valsalva maneuver, while latent RLS occurred when MBs were only detected after the Valsalva maneuver. Two ultrasound technologists were designated to assess the extent of RLS and the RLS type in all subjects for whom migraine had been diagnosed by a neurologist.
2.3. MRI Examination. In this test, a Siemens Avanto 1.5T superconducting MR imaging system and head quadrature coil were used, including T1WI, T2WI, and fluid attenuated inversion recovery (FLAIR) images. The scan parameters were as follows: T1WI used fast spin echo sequence, TR: 550ms and TE: 8.4ms; T2WI used fast spin echo sequence, TR: 4500ms and TE: 85ms; FLAIR used inversion recovery sequences, TR: 9000ms, TE: 103ms, TI: 2500ms, thickness 6 mm, interval 1.2 mm, matrix 256 × 256, and field of view 230mm× 230 mm. Two neuroimaging specialists interpreted the MRI results to measure the existence of silent lacunar infarcts using double-blinded methods. We defined asymptomatic lacunar infarcts as hyperintense lesions on T2WI, with corresponding hypointense lesions with a hyperintense rimon FLAIR, located in the basal ganglia, thalamus, internal or external capsule, or brain stem with a diameter <20mm and not compatible with clinical findings.
2.4. Statistical Analysis. The data obtained were analyzed using SPSS 17.0 statistical software. A two-sample ??-test was applied to compare the difference between patients and controls. The chi-square test was used to compare the risk factors between patients and controls, including gender, hypertension, diabetes, coronary heart disease, hyperlipidemia, and smoking history. A two-tailed ?? value of <0.05 was considered to be statistically significant.
3. Results
3.1. Baseline Demographics. In total, 263 patients with migraine who simultaneously met our inclusion and exclusion criteria were enrolled in our study during January 2010 to December 2011. Among them, 127 patients fell into RLS group while 136 were in the non-RLS group. The average age of the patients was 39.8 ± 13.4 years in the RLS group and 37.2 ± 13.6 years in the non-RLS group. The male to female ratio was 49:78 in RLS group and 62:74 in non-RLS group, respectively.The mean age and sex ratio between the two groups were not significantly different (?? > 0.05). In addition, incidence of the common risk factors of ischemic stroke (hypertension, diabetes, hyperlipidemia, and smoking history) was not found to be statistically significantly different between the RLS and non-RLS groups, shown in Table 1 (?? > 0.05).
3.2. RLS Did Not Increase the Incidence of Silent Lacunar Infarct in Patients with Migraine. Among the 127 migraine patients with RLS, silent lacunar infarcts were identified in 32 patients (25.2%), whereas 29 out of the 136 patients (21.3%) were found to have silent lacunar infarcts in the non-RLS group. The prevalence of silent lacunar infarcts in the RLS group was similar to the non-RLS group (?? > 0.05), as demonstrated in Table 2. Taken together with the fact that the mean ages, sex ratio, and the common vascular risk factors between RLS group and non-RLS group were comparable, RLS did not significantly increase the incidence of silent lacunar infarcts in patients with migraine.
3.3. Incidence of the Silent Lacunar Infarcts in Migraine Patients with RLS Was Similar Regardless of the Type of RLS. In addition, the RLS group (127 subjects) could be subdivided into permanent RLS (77 subjects) and latent RLS (50 subjects). The incidence of silent lacunar infarcts seen by MRI in the permanent RLS and latent RLS subgroups was 22/77 (28.6%) and 10/50 (20%) which was comparable with the nonshunt RLS group (28.6% versus 20% versus 21.3%, ?? > 0.05), as demonstrated in Figure 1(a). In addition, according to the count of MBs detected by the TCD bubble test, the RLS group could be subdivided into mild-shunt and large-shunt groups. We further investigated the prevalence of silent lacunar infarcts in the non-RLS group (i.e., nonshunt group), mild-shunt group, and largeshunt group,which was 21.3%, 23.8%, and 29.3%, respectively, shown inFigure 1(b).Although the incidence of silent lacunar infarcts was higher in the large-shunt group; however, it did not reach a significant difference (?? > 0.05). Collectively, different types of RLS contributed equally to the incidence of the silent lacunar infarcts visible by MRI in patients with migraine.
3.4. RLS Did Not Increase the Incidence of Silent Lacunar Infarcts in Older Patients with Migraine. Previous studies have found that the prevalence of silent lacunar infarcts increases with age [9, 10]. All the patients enrolled in this study were divided into one of two groups: ≥50 years or <50 years. They were then subdivided into RLS and non- RLS subgroups based on the existence of RLS in both age groups.We compared the prevalence of silent lacunar infarcts between the RLS and non-RLS subgroups, both for the ≥50 years and the <50 years age groups. Table 3 shows the prevalence of silent lacunar infarcts in the RLS and non-RLS subgroups, respectively, as well as the ≥50 years and <50 years age groups. We found that the prevalence of silent lacunar infarcts in patients with RLS (i.e., the RLS subgroup) was higher in the ≥50 years age group than the <50 years age group (53.1% versus 15.8%, ?? < 0.05); however, it did not differ from that of the non-RLS subgroup in the ≥50 years age group (53.1% versus 37.5%, ?? > 0.05).Therefore, RLS did not increase the incidence of silent lacunar infarcts in older patients with migraine.
