Localization Of Infratentorial Lesion Could Predict Patent ForamenOvale As An Etiology in Embolic Stroke Of Undetermined Source Ⅱ

Results

A comparison of patient characteristics and PFO between the infratentorial lesion and non-infratentorial lesion groups is shown in Table 1. The median NIHSS score(1 [interquartile range, 0-4]versus 1[interquartile range, 1-2], respectively; p=0.041) and an E/e ratio of>14(37.0% versus 14.9%, respectively; P=0.022) were higher in patients of the infratentorial lesion group than in those of the non-infratentorial lesion group, The prevalence of chronic kidney disease tended to be higher in patients of the group than in those of the noninfratentorial group(33.3% versus 16.4%respectively; P=0.068). There was no difference in the prevalence of complex aortic atheroma between the non-infratentorial lesion and infratentorial lesion groups (19.4% versus 29.6%;P=0.362). One patient with non-infratentorial lesions had both PFO and complex aortic atheroma, whereas, in patients with infratentorial lesions, no patient had both PFO and complex aortic atheroma. The prevalence of PFO(40.7%versus 14.9%, respectively; P=0.007)especially large PFO (30.0% versus 3.0%, respectively; P<0.001), was significantly higher in patients of theinfratentorial lesion group than in those of the non-infratentorial lesion group. A comparison of patient characteristics and PFO between small infarcts and medium/large infarcts is shown in Table 2. Median NIHSS on admission (2[interquartile range, 1-3] versus 1 [interquartile range,0-2], respectively; p=0.015) and left atrial appendage flow (53.8+13.4 cm/s versus 60.7+16.0 cm/s, P=0.029)were significantly higher in patients with large infarcts than in those with the small infarct group, There was no difference in the prevalence between the two groups (27.1% versus 17.4%, respectively; P= 0.06).

Cistanche Supplement Support Kidney Function Supplement

A comparison of patient characteristics and PFO between single lesions and multiple lesions is shown in Table 3. The prevalence of chronic kidney disease was significantly higher in patients of the multiple lesion group than in those of the single lesion group(38.7% versus 12.7%, respectively; P=0.005)Furthermore, the prevalence of LAD enlargement was higher in patients of the multiple lesion group than in those of the single lesion group (28.6% versus 39.0%, respectively; P=0.012). Comparison of RoPE score between single lesion and multiple lesion groups showed that the probability of a RoPE score >5 points tended to be higher with multiple lesions than with single lesions(group prevalence, 28.6% versus 14.3%). Comparison of the RoPE score between groups showed that the probability of a RoPE score >5 points tended to be higher with large infarcts than with small infarcts(group prevalence, 37.5% versus 15.4%). Comparison of Rope score between groups showed that the probability of a RoPE score >5 points tended to be higher in the infratentorial lesion group than in the-infratentorial lesion group((group prevalence,36.4% versus the 10%) probability of a RoPE score >5 points tended tobe higher in the infratentorial lesion group than in the-infratentorial lesion group((group prevalence,36.4% versus 10%).

Comparison of PFO size (large or small/moderate PFO)with infarct location, size, and number are shown in Fig.2. The prevalence of infratentorial lesions was higher in large PFO than in small/moderate PFO(80.0% versus 20.0%respectively; P=0.016). However, there was no relationship between PFO size and infarct size or number. In contrast to PFO, the presence of complex aortic atheroma was not related to infarct size, location, or number (Tables 1, 2, and 3). Multivariate logistic regression analysis (Table 4) demonstrated that the prevalence of PFO was an independent predictor of location in the infratentorial lesion (OR.2.16; 95% CI, 1.23-3.89; P=0.008)

Discussion

After adjustment for possible confounding factors, the infratentorial lesion was associated with the presence of PFO in patients with ESUS. We further showed that large PFO was associated with a higher likelihood of developing infratentorial lesions than small/moderate PFO, Regarding lesion size, left atrial appendage flow velocity was significantly lower in patients with small lesions than in those with large lesions via univariate analysis, although the difference became non-significant after multivariate adjustments. On the other hand, the number of lesions was not associated with baseline characteristics or echocardiographic findings. 

Identifying etiologies of ESUS should be important in determining secondary prevention strategies because several types of potential sources of embolism are established with ESUS. Among them, PFO-related stroke is one of the most important causes in patients with ESUS, Thus far, some studies have investigated the associations between infarct patterns and PFO-related stroke among patients with cryptogenic stroke. For example, Thaler et al. explored whether there are radiological variables that are associated with PFO in patients with cryptogenic stroke according to the TOAST classification. They described that large and superficially located strokes, which were defined as involving the cerebral or cerebellar cortex, were likely to be PFO-associated14. Furthermore, Kim et al.'s research targeted PFO.-associated stroke among patients with cryptogenic stroke and investigated the characteristics of lesion patterns by MRlto compare them with atria. fibrillation-associated stroke. They defined cryptogenic stroke by the TOASlclassification or as highly suspicious of cryptogenic embolic source. They identified that PFO-associated stroke was more frequently observed as single cortical infarctions (34.2% versus 3.1%;P<0.001)0multiple small(<15 mm)scattered lesions in the same territory(23.1%6 versus 5.9%;P<0.001) and the vertebrobasilar artery territory(44.4%6 versus22.9%6) than atrial fibrillation-associated stroke15). Heet al. also demonstrated that PFO-related strokes in cryptogenic stroke patients were observed as having posterior circulation and small size(<10 mm)16They defined cryptogenic stroke as having a stroke without a confirmed reason after thorough work-upCerebral infarctions in the PFO group were located more in the posterior circulation(42.3%), whereas most lesions in the negative PFO group were located in the anterior circulation (59.7%,p<0.01)Concerning lesion size, the proportion of patients with small lesion size(<10 mm) was much higher in the PFO group(76.6%)than in the negative PFOgroup(48.8%, P<0.001). The findings of the studies that PFO.-related stroke is more frequently observed in the vertebrobasilar artery territories concur with our results, On the other hand, Jauss et/. could not indicate the features of neuroimaging in 73 subjects with PFO-associated stroke and cryptogenic stroke without PFO. They defnedcryptogenic stroke as having no evidence of camtidstenosis, other apparent stroke causes such as dissection, vasculitis, or an apparent embolic source (atrial fibrillation, aortal plaques, dilated ventricle, other cardiac embolic sources, etc.).Furthermore, they excluded patients whose work.up data incomplete. The results indicated that it was not possible to discriminate between cryptogenic stroke and stroke from an assumed PFO-associated stroke17)

Such discrepancy might be partly explained by the usage of different criteria for cryptogenic stroke study. The reason for this may be due to the fact that no generally accepted definition exists for cryptogenic stroke, ESUS is a clinical construct that can eliminate 

this problem is because of established diagnostic criteria and our study is one of the few studies that attempt to identify the relationship between neuroimaging and presumed PFO-associated stroke in patients with Jesus.

Several mechanisms by which PFO-related strokes are frequently located in infratentorial lesions have been suggested. The relationship between infratentorial lesions and PFO-associated stroke is still not completely understood, although several mechanisms have been suggested. A previous study)using radionuclide venography revealed excess flow to the vertebrobasilar circulation after the Valsalvamaneuver in patients with PFO18), Becauseparadoxical embolisms also need the right-to-left shunt (RLS)to be opened by the Valsalva maneuver, the increased blood flow to the pertinent territory after the maneuver may explain the high incidence of ischemic lesions in the vertebrobasilar circulation inPFO-associated stroke. Vertebrobasilar circulation receives less adrenergic innervation19). When the sympathetic tone is increased by the Valsalvamaneuver, vertebrobasilar circulation, which is less responsive to sympathetic stimuli, increases blood flow, This may increase the likelihood of blood clot formation after increased blood flow to the vertebrobasilar circulation after passage through the thePFO.Hayashida et al. used(99m)Tc-MAA to monitor the passage of blood flow through the PFOand they found that posterior circulation exceeds anterior circulation by 16.1% under the Valsalvamaneuver 18)

There are some limitations in this study. First, our study was conducted in a single-center setting and had relatively lower power. Second, since the study excluded 96 patients among 190 patients, it could have potentially led to selection bias. This was primarily because elderly patients, those who had severe neurologic symptoms, or those who died of index stroke acutely and who could not undergo TEE, might have been excluded from the analysis. Third, the diagnostic workup for the venous thrombosis was not fully investigated. This means our patients with PFO might not have had a paradoxical embolism. However, as far as we have examined, the patients with ESUS who we detected with PFO by TEE did not have other potential causes of stroke. Therefore, it is not a gross exaggeration to say that their causes were likely due to a paradoxical embolism. Fourth, in our study, all patients who underwent TEE did not necessarily undergo transcranial echocardiography(TCD)to assess RLS. TCD is widely known to be highly sensitive and noninvasive for RLS diagnosis, therefore, it is useful as a screening tool. Although TCD could not be performed for all patients with Jesus in the present study, TEE was performed with high accuracy because systemic sedation was not used, and microbubble testing was conducted three times under the Valsalva maneuver of sufficient intensity. Fifth, although our study suggested that infratentorial lesions are associated with PFO-related strokes, the RoPE score was not particularly high in patients with PFO in the infratentorial lesion group. However, in cases where PFO was detected by TEE, patients underwent adequate examinations to exclude other potential causes of strokes, and we confirmed no apparent cause. Furthermore, the RoPE score is a probability index; thus, low scores cannot exclude with certainty the possibility of PFO-attributablestroke, while higher scores cannot confirm the causative relationship. Further studies involving more patients are needed for verification.

Conclusion

The infratentorial lesion is independently associated with PFO in patients with ESUS. Further multicenter studies involving a larger number of patients are warranted to verify our results.

Acknowledgments

None.

Sources of Funding

None.

Conflicts of Interest

Dr. Kitagawa reports grants and personal fees from Daiichi Sankyo, grants and personal fees fromKyowa Hakko Kirin, grants and personal fees from Bayer Inc, grants and personal fees from Sanofi, grants and personal fees from Nippon Boehringer Ingelheim, grants and personal fees from Takeda Pharmaceuticalgrants and personal fees from Sumitomo. DainipponPharma, and personal fees from Astellas Pharma outside the submitted work.

References

1)Hart RG, Diener HC, Coutts SB, Easton JD, Granger CB, O'Donnell M, Sacco RL, Connoly S]. Embolicstrokes of undetermined source: The case for a new clinical construct.Lancet Neurol,2014;13:429-4382)Bang OY, Lee M, Ryoo S, Kim S], Kim Jw. PatentForamen Ovale and Stroke-Current Status. . Stroke,2015:17:229-237

3) Mas JL, Arquizan C, Lamy C, Zuber M, Cabanes LDerumeaux G, Coste ]. Recurrent cerebrovascular events associated with patent foramen ovale, atrial septa. aneurysm, or both.N.Engl. J.Med, 2001;345:1740-17464) Lamy C, Giannesini C, Zuber M, Arquizan C, Meder JETrystramD,Coste J,Mas Jl. Clinical and Imaging Findings in Cryptogenic Stroke Patients With and Without Patent Foramen Ovale: the PFO-ASA StudyAtrial Septal Aneurysm.Stroke,2002;33:2149-21505)Adams H, Bendixen B, Kappelle L, Biller J, Love B, Gordon D, Marsh 3rd E. Classification of Subtype of Acute Ischemic Stroke.Stroke,1993;23:35-416)Lang RM, Bierig M,Devereux RB, Flachskampf FA,Foster E, Pellikka PA, Picard MH, Roman M, Seward ].Shanewise JS, Solomon SD, Spencer KT, Sutton MSStewart W. Recommendations for chamber quantification: A report from the American Society ofEchocardiography's guidelines and standards committee and the Chamber Quantification Writing Group, developed in conjunction with the European AssociationofEchocardiograph.J.Am.Soc,Echocardiogr, 2005;181440-14637)Nagueh SF,Smiseth OA, Appleton C, Byrd BFDokainish H,Edvardsen T,Flachskampf FA, GillebertCT, Klein AL, Lancellotti P Marino P Oh JK, PopescuBA, Waggoner AD. Recommendations for the Evaluation of Left Ventricular Diastolic Function by Echocardiography: An Update from the American Society of Echocardiography and the European Association cardiovascular Imaging.J. Am. Soc. Echocardiogr, 2016;29:277-314