摘自：BMC Neurology (2018)
作者：Xiao-han Jiang, Si-bo Wang, Qian Tian, Chi Zhong, Guan-ling Zhang, Ya-jie Li, Pan Lin, Yong You,Rong Guo, Ying-hua Cui and Ying-qi Xing*
Abstract
Background: Migraine is considered as a risk factor for subclinical brain ischemic lesions, and right-to-left shunt(RLS) is more common among migraineurs. This cross-sectional study assessed the association of RLS with the increased prevalence of subclinical ischemic brain lesions in migraineurs.
Methods: We enrolled 334 migraineurs from a multicentre study from June 2015 to August 2016. Participants were all evaluated using contrast-enhanced transcranial Doppler, magnetic resonance imaging (MRI), and completed a questionnaire covering demographics, the main risk factors of vascular disease, and migraine status. RLS was classified into four grades (Grade 0 = Negative; Grade I = 1 ≤ microbubbles (MBs) ≤ 10; Grade II = MBs > 10 and no curtain; Grade III = curtain). Silent brain ischemic infarctions (SBI) and white matter hyperintensities (WMHs) were evaluated on MRI.
Results: We found no significant differences between migraineurs with RLS and migraineurs without RLS in subclinical ischemic brain lesions.SBI and WMHs did not increase with the size of the RLS(p for trend for SBI = 0.066, p for trend for WMHs = 0.543). Furthermore, curtain RLS in migraineurs was a risk factor for the presence of SBI (p = 0.032, OR = 3.47;95%CI: 1.12−10.76). There was no association between RLS and the presence of WMHs.
Conclusion: Overall, RLS is not associated with increased SBI or WMHs in migraineurs. However, when RLS is present as a curtain pattern, it is likely to be a risk factor for SBIs in migraineurs. Trial registration: No. NCT02425696; registered on April 21, 2015.
Keywords: Infarction, Magnetic resonance imaging, Migraine, Patent foramen ovale, Transcranial Doppler ultrasonography,White matter
Background
Migraine, which is the most common type of primary headache encountered in the clinic, affects daily life and even causes ischemic events in sufferers. The relationship between migraine and subclinical brain ischemic lesions, including silent brain infarctions (SBI) and white matter hyperintensities (WMHs) on agnetic resonance imaging (MRI), is complicated and disputed [1–5].Several studies ave reported that SBI and WMHs were also more prevalent in subjects with migraine [1, 3, 6], especially migraine with aura (MA) [2, 7].
Furthermore, right-to-left shunt (RLS) may be a shared risk factor in migraine and subclinical brain ischemic lesions. The relationship between RLS and migraine has been widely investigated [8–10]. Several case−control analyses have indicated that RLS is more common in patients who suffer MA than normals [10, 11]. RLS, and particularly large RLS, caused mainly by a patent foramen ovale (PFO) [12], is also considered to be a cause of cryptogenic stroke (CS) in young patients [13]. Nevertheless, the role of RLS in migraineurs with subclinical brain ischemic lesions remains uncertain. To investigate whether RLS is an etiological factor for subclinical brain ischemic lesions in migraineurs, we cooperated with eight other centres to collect subjects for uniform assessment of subclinical ischemic brain lesions in migraineurs with and without RLS by MRI. In the present study, we evaluated whether, in migraineurs, (1) RLS per se, or a particular size/subtype of RLS, is associated with a higher incidence of SBI and WMHs; (2) RLS is associated with increased SBI located in the posterior circulation; (3) deep WMHs (dWMHs) is more commonly present in subjects with RLS than those without RLS.
Methods
Study population The study procedures were approved by the Ethics Committee of the First Hospital of Jilin University (clinical trial no. NCT02425696; registered on April 21, 2015).All patients provided written informed consent prior to participation. All methods were carried out in accordance with the approved guidelines.
From June 2015 to August 2016, we consecutively enrolled patients from nine medical centres in China; the patients were aged between 18 and 70 years, and were diagnosed with migraine through a questionnaire based on the International Classification of Headache Disorders,3rd edition beta version (ICHD-3beta;Headache Classification Committee of the International Headache Society, 2013). All subjects have underwent neurological examination and were screened by transcranial Doppler (TCD), contrast-enhanced TCD (c-TCD), MRI, and a questionnaire to obtain information on demographic characteristics, the main risk factors of vascular disease,and migraine status. The main risk factors of vascular disease include body mass index (BMI), hypertension,diabetes, heart disease (including atrial fibrillation and coronary heart disease), and smoking status.Patients with the following characteristics were excluded: (1) intracranial or extracranial artery stenosis or occlusion; (2) incomplete MRI or c-TCD, an insufficient temporal window, or who could not perform the Valsalva manoeuvre (VM) due to cognitive disorder, or severe heart or lung disease.
c-TCD protocol
c-TCD examinations were performed by using a handheld 2-MHz probe connected to the TCD detector (EMS-9A or 9 PB, Delica, China). The procedure was performed by experienced ultrasound technologists blinded to migraine diagnosis and MRI findings. Before the test, patients were asked to practice a standardized VM. Briefly, an 18-gauge catheter was inserted into the patient’s right antecubital vein. Contrast agent was prepared, using 9 ml isotonic saline solution, 1 ml of air, and a drop of the patient’s blood, which was mixed vigorously between two 10-ml syringes through a threeway stopcock, and was injected with the participant in the supine position [14]. After 30 mixing cycles, the contrast agent was injected as a rapid bolus while insonating the left middle cerebral artery (MCA) through the temporal bone window. The insonation lasted 20 s from the injection. The procedure was carried out three times: in the first measurement, injection was performed during normal espiration to detect any permanent RLS. The second and third injections were performed 5 s prior to the start of a 10-s VM. The time interval between injections was at least 5 min. The maximum number of microbubbles (MBs) was taken as the estimate of the maximum degree of shunt, which was recorded separately from the MCA during rest and after the VM [15]. On the basis of the standards reported by Serena et al., Jauss et al., and Yang et al. [15–17], a four-level RLS categorization, based on the MB count, was applied as follows: Grade 0 = Negative;Grade I = 1 ≤ MBs ≤ 10; Grade II = MBs > 10 and no curtain;Grade III = curtain (Fig. 1). RLS was considered permanent if it occurred during rest, and latent if it only occurred after a VM.
