Clinical And Imaging Characteristics Of Cryptogenic Stroke With Patent Foramen Ovale

BackgroundCryptogenic stroke(CS)is clinically defined as ischemic stroke in which the specific etiology and mechanism leading to the stroke remain undetermined after examination.With the development and advancement of diagnostic technology,some uncommon causes of CS have been gradually discovered.Most CS still results from undetected cardiac factors,among which the paradoxical embolism caused by patent foramen ovale(PFO)is one of the most important pathogenesis of CS.Foramen ovale is a normal physiological channel of left and right atrium during fetal period.If it remains incompletely fused after 3 years of age,this can be termed as PFO.A variety of methods can be used to screen and evaluate PFO,among which the contrast-enhanced transcranial Doppler(c-TCD)is expected to be the first choice to screen PFO.Right-to-left shunt(RLS)induced by a patent foramen ovale(PFO)is associated with cryptogenic stroke(CS).However,the relationship between the amount of RLS and the stroke pattern is still unclear.Current treatments of Stroke associated with PFO mainly include medical therapy and percutaneous interventional closure.With the development of interventional technology,PFO closure has become a hotspot of current research.More and more studies have shown that PFO closure shows high safety and effectiveness in the secondary prevention of CS.But there are still some problems,such as the indications of PFO closure,the comparison of the efficacy of anticoagulants and antiplatelet therapy and so on.A large number of randomized controlled trials are still needed.ObjectiveTo evaluate the clinical characteristics of these patients with different amounts of RLS and analyze the relationship between the amount of RLS and the RoPE score as well as the relationship of the amount of RLS and the stroke pattern.so as to help make the correct diagnosis of PFO related ischemic stroke and choose the best secondary prevention strategy for patientsMaterial and methodsWe retrospectively investigated 38 patients with CS and PFO who were admitted to Qilu Hospital of Shandong University from 1st January 2018 to 31st January 2021.PFO was determined by means of contrast-enhanced transcranial Doppler(c-TCD)and transesophageal echocardiography(TEE).Collecting the relevant clinical data of the patients,the semi-quantitative classification of RLS were obtained by c-TCD and to compare the detection rates of RLS among different examination.The patients were divided into 2 groups according to the amount of right-to-left shunt.The clinical and imaging characteristics of the two groups were compared and analyzed,as well as the risk of paradoxical embolism(RoPE)score,and the relationship between the amount of RLS and the RoPE score was also examined.Results1.Baseline characteristics:There were 24 patients in small RLS group and 14 patients in large RLS group.35(92.1%)were male while 3(7.9%)were females,with an average age of 46.97±15.04.The prevalence of hypertension in large RLS group was higher than that in small RLS group(P<0.001).There was no significant difference in age,gender and the prevalence of diabetes,coronary atherosclerotic heart disease,hyperlipidemia,hyperhomocysteinemia,previous stroke/TIA history,migraine history,smoking and drinking history between the two groups(P>0.05)2.Laboratory examination:Hemoglobin(Hb),platelet count(PLT),mean platelet volume(MPV),neutrophil to lymphocyte ratio(NLR),platelet to lymphocyte ratio(PLR),fibrinogen(Fib),D-dimer,fasting blood glucose,serum lipids and homocysteine(Hcy)all showed no significant difference in two groups(P>0.05).3.Evaluation of RLS:There were 9 cases of potential shunt and 29 cases of inherent shunt,including 12 cases(31.6%),12 cases(31.6%),8 cases(21.1%)and 6 cases(15.8%)of grade Ⅰ,Ⅱ,Ⅲ and Ⅳ RLS respectively.The proportion of potential shunt and inherent shunt between small RLS group and large RLS group was of no difference(P>0.05).All patients underwent c-TTE and c-TEE examination.The positive rates of c-TTE and c-TEE examination were 87.5%and 79.2%in the small shunt group,which were both 92.9%in the other group,respectively(P>0.05).There were 19 cases(65.6%)with grade Ⅰ shunt,4 cases(13.8%)with grade Ⅱ shunt,4 cases(13.8%)with grade Ⅲ shunt and 2 cases(6.9%)with grade IV shunt and the detection rate of c-TCD,c-TTE and c-TEE was 76.3%,57.9%and 44.7%at resting state at resting state.While there were 12 cases of grade Ⅰ(31.6%),12 cases of grade Ⅱ(31.6%),8 cases of grade Ⅲ(21.1%)and 6 cases of grade Ⅳ shunt(15.8%),and the detection rate of c-TCD,c-TTE and c-TEE was 100.0%,89.5%,84.2%during Valsalva maneuver,respectively.The detection rate of RLS as well as the semi-quantitative classification of RLS during Valsalva maneuver were higher than those at resting state(P<0.05).4.Neuroimaging Assessment:Single infarction and multiple infarction accounted for 45.8%and 54.2%respectively in small RLS group.While in large shunt group,both of two kinds all accounted for 50.0%.In the small shunt group,cortical,subcortical and cortical-subcortical infarction accounted for 4.2%,79.2%and 16.7%respectively.In the large shunt group,cortical,subcortical and cortical-subcortical infarction accounted for 14.3%,71.4%and 14.3%respectively.Moreover,unilateral anterior infarction,bilateral anterior,posterior,and anterior with posterior circulation accounted for 45.8%,41.7%,25%and 12.5%respectively,which are 42.9%,7.1%,28.6%and 21.4%in large shunt group.The number,location or vessel distribution of infarction between small RLS group and large RLS group were all of no statistical significance(P>0.05)5.The score of RoPE and the correlation between RoPE score and the amount of RLS:The average RoPE score was 5.92±1.98 in the small RLS group and 5.57±1.60 in the large RLS group,with no significant difference.And there was no significant correlation between RLS and rope score(r=-0.095,P=0.570)Conclusion1.Cryptogenic stroke patients with PFO are usually younger,most are males and less with traditional cerebrovascular risk factors.2.The c-TCD is not only noninvasive and reproducible,it can also make semi-quantitative classification of RLS,greatly reducing the pain and complications caused by transesophageal ultrasound.It can be used as the preferred method for screening PFO in clinical work.3.Valsalva maneuver can improve the detection rate of PFO and the semi-quantitative classification of RLS.4.The proportion of single and multiple infarction is similar,but subcortical infarction are most common in PFO related stroke.The amounts of right to left shunt do not affect the number,location and vascular distribution of infarction.5.The RoPE score is used to evaluate the correlation of PFO and CS,but the amounts of RLS do not influence the RoPE score,and there was no correlation between the RoPE score and the RLS.