Crossed cerebellar diaschisis worsens the clinical presentation in acute large vessel occlusion

Crossed cerebellar diaschisis worsens the clinical presentation in acute large vessel occlusion | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article Crossed cerebellar diaschisis worsens the clinical presentation in acute large vessel occlusion Anissa Abderrakib, Noemie Ligot, Nathan Torcida, Niloufar Sadeghi, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-1821086/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background and Purpose Initial NIHSS in anterior large vessel occlusion (LVO) correlates partially with the hypoperfusion volume. We aimed at assessing the contribution of crossed cerebellar diaschisis (CCD) from the hypo-perfused territory on LVO initial clinical deficit. Method CCD was retrospectively identified by brain CT perfusion imaging (CTP) in patients with anterior LVO treated by mechanical thrombectomy (MT) from January 2017 to July 2021. CCD was defined by CTP parameters alteration in contralateral cerebellar hemisphere to the LVO. NIHSS, clinical/perfusion variables and CCD were included in regression models to assess their inter-relationships. Results 206 patients were included. CCD was present in 90 patients (69%). NIHSS scores were higher on admission and at stroke discharge among patients with CCD (17.90 ± 6.1vs 11.4 ± 8.4, p <0.001; 9.6 ± 7.7 vs 6.6 ± 7.9, p = 0.049 respectively). Patients with a CCD had higher stroke volumes (118.2 ± 60.3 vs 69.3 ± 59.7, p<0.001) and lower rate of known atrial fibrillation (22 % vs 41%, p = 0.021). On multivariable logistic regression, CCD independently worsened initial NIHSS (OR 4.85 (2.37-7.33); p<0.001). Conclusion CCD is found in 69% of LVO on admission CTP, correlates with stroke volumes and independently worsens initial NIHSS. NIHSS Large vessel occlusion Crossed cerebellar diaschisis Perfusion stroke outcome & thrombectomy Figures Figure 1 Figure 2 Figure 3 Introduction The National Institutes of Health Stroke Scale (NIHSS) is a graded neurological examination that has become the gold-standard for clinical assessments in ischemic stroke trials since the intravenous recombinant tissue plasminogen activator (t-PA) trial for ischemic stroke in 1995. 1,2 NIHSS is highly reliable across raters from different medical specialties and is now the the most widely used deficit rating scale in modern neurology. 2 In anterior circulation stroke, admission NIHSS correlates with both stroke volume 3–5 and outcome 6 and has become a surrogate to assess initial stroke severity. Change in NIHSS score from baseline to 24 h is part of the evaluation of the efficiency of recanalization therapies. 7,8 However, while there is a correlation between the initial NIHSS and the hypo-perfused brain tissue downstream to the occlusion of a cerebral artery, the correlation is only partial with Spearman’s r correlation coefficient ranging from 0.48 to at best 0.68. 3–5 Thus, part of initial NIHSS severity in acute stroke relates to other potential mechanisms than the dysfunction of a brain vascular territory. Diaschisis, a functional impairment of brain areas remote from a cerebral lesion to which it is functionally connected could contribute to initial NIHSS severity and explain the apparent dichotomy between patients ‘deficits and the hypo-perfused brain area. Diaschisis was first described by Von Monakow in 1914, to explain a functional impairment of a structurally normal areas as a result of remote, but connected lesion to the affected area. 9 Diaschisis is associated to a matched depression of blood flow and metabolism between the injured brain area and its connected counterparts. 10 In stroke, transhemispheric, 11,12 thalamic, 13 internal capsule 14,15 and cerebellar diaschisis 16–18 have been described at both acute and chronic stages. Yet, the relation between diaschisis and initial stroke severity is seldom described. In anterior large vessel occlusion (LVO), the crossed cerebellar diaschisis (CCD) could likely contribute to LVO initial clinical deficit. Indeed, cerebello-cortical connectivity supports motor, cognitive and perceptual functions 19 thanks to reciprocal connections between the cerebellum, motor, parietal and prefrontal cortices. 20,21 Furthermore, CCD is associated to clinical impairments in both acquired and degenerative neurological diseases. 22–24 After ischemic stroke, CCD has been reported in several studies using different techniques Single photon emission computerized tomography (SPECT), 22 Positron Emission Tomography (PET), 17,18 MRI perfusion imaging 25 and perfusion CT imaging (CTP) 16,26 with a prevalence ranging from 15% 25 to 58%. 17 The bulk of those studies focused on the relation between stroke volumes and CCD 26 or on stroke volumes and long term outcomes. 22,25,26 Only one study focused on the role of CCD in acute stroke symptoms and its relation to admission NIHSS using 15 O-water brain PET on 19 patients. This study found a parallel improvement of CCD volume and NIHSS when serially and simultaneously assessed at admission, three and twenty-four hours post thrombolysis. 18 Yet, the results those studies must be balanced by the fact that they included proximal and distal vessel occlusion and were realized before mechanical thrombectomy was validated for LVO. Here, we aim at determining, using CTP in a large cohort of anterior circulation LVO who underwent mechanical thrombectomy (MT), (i) the prevalence of CCD in acute anterior LVO, (ii) the part of the initial clinical deficit explained by CCD and (iii) the factors associated with the presence of a CCD using logistic regression models. Results a. Study population 296 patients benefited from MT in the period considered. 75 patients lacked CTP on admission, 34 patients had LVO in posterior circulation, intracranial stenosis or other abnormalities preventing interpretation and in 56 cases, CTP was judged either incomplete or uninterpretable preventing optimal evaluation of CCD. Finally, 131 patients were included (figure 1). Main characteristics of the population are detailed in (table 1). b. CCD prevalence and characteristics Ninety patients out of 131 (69%) had a CCD. Patients with CCD displayed significantly higher NIHSS on admission and at stroke discharge (17.90 ± 6.1 vs 11.4±8.4, p < 0.001; 9.6 ± 7.7 vs 6.6 ± 7.9, p = 0.049 respectively). Patients presenting with CCD had higher hypoperfusion volume (118.2 ± 60.3 vs 69.3 ± 59.7, p < 0.001). Known atrial fibrillation (KAF) was present in 19 patients out of 87 (22%) in the CCD group while in 17 out of 41 patients (41%) without CCD ( p = 0.021). Other demographic and clinical data are illustrated in the Table 1. Figure 2. illustrates a typical CCD. --- Insert table 1 about here --- Logistic regression model for the occurrence of a CCD (table 2) The multiple linear regression model including age, NIHSS at admission, ischemic core volume, ischemic penumbra volume and known atrial fibrillation was statistically significant to predict the occurrence of a CCD treatment (Nagelkerke determination coefficient, R 2 = 0.366, χ2 (degrees of freedom(dof):120, 38.4, p < 0.001) and explained 37 % of CCD occurrence. In this model KAF independently accounted for 7% the outcome variability when age, hypoperfusion volume, core volume and NIHSS at admission were included in the null model as nuisance parameters. --- Insert table 2 --- Linear regression model for admission NIHSS (table 3) The multiple linear regression model including age, CCD, ischemic core volume, ischemic penumbra volume and known atrial fibrillation was statistically significant to predict admission NIHSS (R 2 = 0.39, F (5 dof) 16, p < .001) and explained 39% of the variability of the admission NIHSS (R 2 = 0.39). In this model CCD independently accounted for 7% the outcome variability when age, hypoperfusion volume, core volume and KAF were included in the null model as nuisance parameters. --- Insert table 3 about here --- Linear regression model for NIHSS at stroke discharge (table 4) The multiple linear regression model including age, NIHSS at admission, ischemic core volume, ischemic penumbra volume, known atrial fibrillation and CCD was statistically significant to predict NIHSS at stroke discharge (R 2 = 0.23, F (5 dof), 6, p < .001) and explained 23% of the variability of the NIHSS 24 hours post-treatment (Nagelkerke determination coefficient, R 2 = 0.63). In this model CCD was not significantly associated to NIHSS at stroke discharge. --- Insert table 4 about here --- Discussion Main findings from this study are that (i) crossed cerebellar diaschisis occurs in 69 % of patients admitted for acute anterior LVO on CTP, (ii) CCD depends both on admission NIHSS score and hypo-perfused volume downstream of the LVO occlusion and shows an inverse relation with known atrial fibrillation and that (iii) CCD independently worsens admission NIHSS. The findings of this study, albeit limited by its monocentric nature, are likely to be generalizable to other populations of LVO treated by thrombectomy. Indeed, our cohort matches closely the characteristics of the large published series on MT in LVO in terms of age, sex, admission NIHSS and rate of KAF. 8,38 In our cohort, a CCD was observed in 69% of all patients. This proportion parallels the seminal reports on CCD after hemispheric stroke using SPECT following 133 Xe inhalation and 15 O-water brain PET where CCD was found in 42% 39 and 58% 13 respectively. However, the CCD rate, we report, is higher than in MRI perfusion weighting imaging (PWI) or MRI blood oxygenation-level dependent cerebrovascular reactivity (BOLD-CVR) where it was described between 15-44%, 25,40,41 and above the 35% described in the single cohort that used CTP. 16,26 The discrepancies between our study and previous works can be reduced to a common denominator. Indeed, CCD is proportional to the total volume of hemispheric hypo-perfusion, 18,22,26,39,42 a fact corroborated in our study. In the MRI studies, the hypoperfused volume was between 30% 40 and 50% 25 lower than in our cohort explaining the lower proportion of CCD. Differences in hypoperfusion volume fails, however, to explain why the rate of CCD was lower in the German study that also used CTP to detect CCD: hypoperfusion volume and admission NIHSS were of similar magnitude than in our study, reflecting comparable stroke severity. The lower rate of CCD in that cohort could reflect a selection bias relating to a pre-thrombectomy era, with patients included between 2009 and 2014. 16 Indeed, our population matches the clinical characteristics of the LVO population in the Thrombectomy trials and notably, in term of the 28% rate of KAF, 8 contrasting to the other cohort that used CTP had a population where patients had a 52% rate of KAF. 26 This difference in KAF prevalence may explain the lower rate of CCD they report, as we found in our cohort that KAF is significatively associated to lower likelihood of CCD. The relationship between KAF and CCD may relate to the onset of hypoperfusion: brutal in in cardioembolic stroke 43,44 and in more prepared background in LVO due atherosclerotic disease where the LVO often occurs in a context of progressive narrowing of arterial lumen leading to previous relative hypoperfusion. CCD is a process triggered by cerebellar Purkinje cells deactivation from less corticopontine input. The Purkinje cell deactivation leads in turn to lower cerebellar metabolism and bloodflow, 45 a process that begins at the acute onset of LVO but is maximal after several hours. 46 The more progressive onset of hypoperfusion in LVO from non-cardioembolic origin would thus allow a more clear CCD as metabolic and blood flow changes in the cerebellum would have had more time to install. In our study, CCD accounts for 7% of admission NIHSS scores regardless of other factors such as penumbra or core volumes. Therefore, while not associated to a structural lesion, a CCD worsens the initial clinical picture of patients with CCD with by a component potentially fully reversible. The presence of CCD is probably an important parameter to consider for accurate analysis of recanalization therapies efficiency as well as acute functional prognosis. In Studies that assessed the benefit of MT +/- intravenous thrombolysis in anterior LVO, NIHSS improved from 17 to 5, 35,47 in which 10% of the improvement could reflect CCD resolution. This suggest that treatment efficiency studies should control for similar rates of CCD in intervention and non-interventions arms. Furthermore, initial clinical examination of patients suffering from LVO strokes should consider the possible interference caused by secondary cortico-cerebellar loops dysfunction added to LVO direct ischemic damage in cases of disproportionate clinical picture as compared to ischemic lesions. Conclusions Crossed cerebellar diaschisis observed with CTP is a frequent phenomenon in anterior LVO strokes treated by MT. CCD is associated with higher stroke volumes and independently worsens admission NIHSS. CCD should be included in the interpretation of admission NIHSS and treatment efficiency, especially when there is a dichotomy between the expected deficit pertaining to the anterior LVO territory and the patient’s clinical presentation. Further studies are needed to evaluate the mechanisms and the implications of acute cerebellar dysfunction in and anterior LVO. Material And Method a. Study design and population Patients admitted between January 2017 and July 2021 were screened from our stroke registry at Erasmus Hospital in Brussels (Belgium) where all cases of acute ischemic strokes are recorded. 27,28 Inclusion criteria were patients (i) aged over eighteen years-old, (ii) presenting with an acute anterior LVO, defined as an occlusion of the ICA (T-type), MCA (M1 or M2 segments) and ACA (A1 or A2 segments) (iii) with a brain perfusion CT imaging with reliable analysis by Rapid® and SyngoVia® software and (iv) who underwent mechanical thrombectomy (MT). b. Cerebral perfusion imaging and CCD identification Pre-MT imaging included non-contrast brain CT, CT brain/neck angiography and CT brain perfusion (CTP). Ischemic core was defined as brain volume with cerebral blood flow (CBF) under 30% of the CBF of the homologous zone in the contralateral hemisphere. Ischemic penumbra was defined as brain volume with time to maximum (Tmax) contrast product arrival exceeded six seconds. 29 Those volume were automatically computed with Rapid® software. 30 As Rapid® perfusion parameters thresholds may not be sensitive enough to identify a CCD, perfusion parameters were also analyzed using a qualitative approach with another software (Syngo.via®) approved in ischemic stroke management. The following perfusion parameters were assessed, mean transit time (MTT), Tmax, time to drain (TTD), time to peak (TTP), CBF and cerebral blood volume (CBV). CCD was defined as a decrease of CBF and CBV and/ or an increase MTT/ TTP/ TTD or T max parameters in the cerebellar hemisphere contralateral to the LVO, comparatively to the cerebellar hemisphere ipsilateral to the LVO. (figure 1) For subjects to be included, at least three consecutive CTP slices that encompassed the cerebellum were required. Imaging analysis was performed by two independent readers used to brain volume CTP interpretation. If a disagreement between readers occurred, results were discussed collegially. --- Insert figure 1 about here --- c. Acute ischemic stroke care and functional outcomes Acute stroke management and care followed ESO guidelines and are detailed in. 27,31 MT recanalization was graded using the TICI scale. 32 Functional outcomes were evaluated by (i) the NIHSS score on admission and at stroke discharge. Variable definition, group comparisons and regression models Variable of interest were selected based on previous stroke outcome predictive models: Age, 33 NIHSS at admission, 7,34 ischemic core volume, 29 ischemic penumbra volume 35,36 and known atrial fibrillation. 37 Those variables, as well as CCD, were chosen as covariates in a linear regression model to predict NIHSS on admission, NIHSS at stroke discharge and as covariates in a logistic regression model to predict a favourable stroke outcome at 90 days. The relationship between variables/covariates and outcomes was assessed by Nagelkerke correlation coefficient. A value of p < 0.05 was considered statistically significant. Then, to assess the relative weight of CCD on outcome, the other variables were included in the null model as nuisance parameters. A similar approach was used to build a logistic regression model to predict the occurrence of a CCD using the aforementioned variables of interest. Comparisons of selected interest variables between patients with and without CCD were done with a bilateral Student’s T-test. All statistical analysis was performed using Jasp® 16.0. Ethics The study was reviewed and approved by the Ethics Committee of Erasmus Hospital, Brussels, Belgium. Written informed consent for participation was not required for this study in accordance with the national legislation and the institutional requirement. All methods were performed in accordance with the relevant guidelines and regulations. Declarations Acknowledgement: Funding sources: Gilles Naeije is a Postdoctorate Clinical Master Specialists at the FRS-FNRS (Brussels, Belgium). Conflict of Interest Statement No authors report no biomedical financial interests or potential conflicts of interest relating to this work. Authors contributions LN, AA, TN, NG:study design, data collection, analysis, manuscript writing. SN: data collection, analysis. 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Med. 378 , 1573–1582 (2018). Tables Table 1. Comparison of characteristics of acute ischemic stroke patients without CCD (CCD-) and with CCD (CCD+). Overall (n=131) CDD (-) (n=41) CDD (+) (n=90) p Age (mean ± SD) 70.6 ± 14.8 71.1 ±13.8 70.4 ±15.4 0.80 NIHSS Admission (mean ± SD) 15.9 ±7.8 11.4±8.4 17.90 ± 6.1 <0.001* NIHSS Discharge (mean ± SD), n 8.6 ± 8.0 (117) 6.6 ± 7.9 (38) 9.6 ± 7.7(79) 0.049* mRS 90 days ≤ 3 %, n 41% (99) 48% (33) 38% (64) 0.332 Known AF (n, %) 128 17 (41%) 19 (22%) 0.021* Core volume (ml) (mean ± SD), n 26.1 ± 35.7 (129) 13.8 ± 26.4 (40) 31.6 ± 35.7 (89) 0.005 Hypoperfusion volume (ml) (mean ± SD), n 103.1 ± 67.8 (129) 69.3 ± 59.7(40) 118.2 ± 60.3(89) <0.001* * Significant p-value. CCD-, no crossed cerebellar diaschisis; CCD+, presence of a crossed cerebellar diaschisis; SD, standard deviation; mRS, modified Rankin scale; AF, atrial fibrillation. Table 2. Linear regression coefficients for the variables assessed in the prediction model of CCD+. Variables OR 95% CI p - value Age 0.98 0.94 - 1.01 0.17 hypoperfusion volume 1.01 1.00- 1.02 0. 039* Core volume 0.99 0.96- 1.02 0.46 KAF 0.29 0.11- 0.79 0.015* NIHSS A dmission 1.14 1.06 - 1.23 < 0.001* CCD+, presence of a CCD; * Significant p-value. OR, Odd ratio; CI, confidence interval; KAF, known atrial fibrillation. Table 3. Linear regression coefficients for the variables assessed in the prediction admission NIHSS. Variables Coefficient 95% CI p - value Age 0.147 0.07- 0.22 < 0.001* Hypoperfusion volume 0.026 0.01- 0.05 0.02* Core volume 0.014 -0.04 - 0.07 0.625 KAF 1.173 -1.25- 3.60 0.34 CCD+ 4.85 2.37- 7.33 < 0.001* * Significant p-value. CI, confidence interval; V, volume; KAF, known atrial fibrillation; CCD+, presence of a crossed cerebellar diaschisis. Table 4. Linear regression coefficients for the variables assessed in the prediction model of stroke discharge NIHSS. Variables Coefficient 95% CI p - value Age 0.14 0.05- 0.24 0.004* Hypoperfusion volume 0.01 -0.02 -0.03 0.750 Core volume 0.09 0.02 - 0.16 0.017* KAF -0.24 -3.31 - 2.82 0.875 CCD+ 2.01 -1.11 - 5.12 0.204 * Significant p-value. CI, confidence interval; V, volume; KAF, known atrial fibrillation; CCD+, presence of a crossed cerebellar diaschisis. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-1821086","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":119385024,"identity":"1478223a-1d35-41d8-80e7-1d95fb8c273c","order_by":0,"name":"Anissa Abderrakib","email":"","orcid":"","institution":"Université Libre de Bruxelles - Cliniques Universitaires de Bruxelles - Hôpital Erasme","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Anissa","middleName":"","lastName":"Abderrakib","suffix":""},{"id":119385025,"identity":"d30f432f-6721-4bf2-9a9c-db1bbbe6b4e7","order_by":1,"name":"Noemie Ligot","email":"","orcid":"","institution":"Université Libre de Bruxelles - Cliniques Universitaires de Bruxelles - Hôpital Erasme","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Noemie","middleName":"","lastName":"Ligot","suffix":""},{"id":119385026,"identity":"cdbfb64e-411b-4e33-b498-9c90e0d246ea","order_by":2,"name":"Nathan Torcida","email":"","orcid":"","institution":"Université Libre de Bruxelles - Cliniques Universitaires de Bruxelles - Hôpital Erasme","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Nathan","middleName":"","lastName":"Torcida","suffix":""},{"id":119385027,"identity":"e94b0219-1875-4c25-beda-04956b553878","order_by":3,"name":"Niloufar Sadeghi","email":"","orcid":"","institution":"Université Libre de Bruxelles - Cliniques Universitaires de Bruxelles - Hôpital Erasme","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Niloufar","middleName":"","lastName":"Sadeghi","suffix":""},{"id":119385028,"identity":"42c48f14-cf2a-44af-bfa9-fe63a48c6ef5","order_by":4,"name":"Gilles Naeije","email":"data:image/png;base64,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","orcid":"","institution":"Université Libre de Bruxelles - Cliniques Universitaires de Bruxelles - Hôpital Erasme","correspondingAuthor":true,"submittingAuthor":false,"prefix":"","firstName":"Gilles","middleName":"","lastName":"Naeije","suffix":""}],"badges":[],"createdAt":"2022-07-03 15:59:07","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-1821086/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-1821086/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":23915858,"identity":"e11fa872-f3d3-4e98-a1f0-793653d490b6","added_by":"auto","created_at":"2022-07-15 17:58:39","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":41901,"visible":true,"origin":"","legend":"\u003cp\u003eFlowchart of the study\u003c/p\u003e\u003cp\u003e\u003cbr\u003e\u003c/p\u003e","description":"","filename":"Figure1.png","url":"https://assets-eu.researchsquare.com/files/rs-1821086/v1/cf42fb435d8aeca3d9af497b.png"},{"id":23915860,"identity":"be3ccad9-8151-4ff7-9890-5c4620323a1c","added_by":"auto","created_at":"2022-07-15 17:58:40","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":757940,"visible":true,"origin":"","legend":"\u003cp\u003eIllustration of a typical crossed cerebellar diaschisis in a left middle cerebral artery (MCA) occlusion. \u003c/p\u003e\u003cp\u003eCTP maps show a decrease in CBF (a) and CBV (b) as well an increase in T max (c) in the left hemisphere. There is a CCD characterized by a simultaneous decrease CVF (a’) and CBV (b’) but also by an increase of Tmax (c’) in the contralateral cerebellar hemisphere. MRI-DWI confirms the presence only of a left sylvian stroke (d and d’). The left M1 occlusion confirmed by CTA is also illustrated above ((e) with blue arrow). \u003c/p\u003e\u003cp\u003eMCA= middle cerebral artery; CTP= brain CT perfusion imaging; CBF= cerebral blood flow; CBV= cerebral blood volume; T max = Time-to-Maximum; CCD= crossed cerebellar diaschisis: DWI = diffusion weighted imaging; CTA= Computed Tomography Angiography.\u003c/p\u003e\u003cp\u003e\u003cbr\u003e\u003c/p\u003e","description":"","filename":"Figure2.png","url":"https://assets-eu.researchsquare.com/files/rs-1821086/v1/e4f15e28cda5a6910f9719d3.png"},{"id":23915859,"identity":"54942ca7-fa9f-4d7d-aea4-50092d4b74c6","added_by":"auto","created_at":"2022-07-15 17:58:39","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":44472,"visible":true,"origin":"","legend":"\u003cp\u003eIllustrates the relationship between Know atrial fibrillation (KAF), admission NIHSS on and hypoperfusion volume and the presence of CCD. KAF is related to a lower rate of CCD. CCD is correlated to higher perfusion volume and admission NIHSS. \u003c/p\u003e\u003cp\u003e\u0026nbsp;\u003c/p\u003e\u003cp\u003e\u003cbr\u003e\u003c/p\u003e","description":"","filename":"Figure3.png","url":"https://assets-eu.researchsquare.com/files/rs-1821086/v1/4899714d24bb7d74057f30e4.png"},{"id":27650059,"identity":"c5c091e6-c7ab-4d77-aee0-916982f4587e","added_by":"auto","created_at":"2022-10-12 03:29:19","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1097116,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-1821086/v1/382a1ce3-bb4c-4e90-baa5-dc54eaaa9ad7.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Crossed cerebellar diaschisis worsens the clinical presentation in acute large vessel occlusion","fulltext":[{"header":"Introduction","content":"\u003cp\u003eThe National Institutes of Health Stroke Scale (NIHSS) is a graded neurological examination that has become the gold-standard for clinical assessments in ischemic stroke trials since the intravenous recombinant tissue plasminogen activator (t-PA) trial for ischemic stroke in 1995.\u003csup\u003e1,2\u003c/sup\u003e NIHSS is highly reliable across raters from different medical specialties and is now the the most widely used deficit rating scale in modern neurology.\u003csup\u003e2\u003c/sup\u003e In anterior circulation stroke, admission NIHSS correlates with both stroke volume\u003csup\u003e3\u0026ndash;5\u003c/sup\u003e and outcome\u003csup\u003e6\u003c/sup\u003e and has become a surrogate to assess initial stroke severity. Change in NIHSS score from baseline to 24 h is part of the evaluation of the efficiency of recanalization therapies.\u003csup\u003e7,8\u003c/sup\u003e However, while there is a correlation between the initial NIHSS and the hypo-perfused brain tissue downstream to the occlusion of a cerebral artery, the correlation is only partial with Spearman\u0026rsquo;s \u003cem\u003er\u0026nbsp;\u003c/em\u003ecorrelation coefficient ranging from 0.48 to at best 0.68.\u003csup\u003e3\u0026ndash;5\u003c/sup\u003e Thus, part of initial NIHSS severity in acute stroke relates to other potential mechanisms than the dysfunction of a brain vascular territory. Diaschisis, a functional impairment of brain areas remote from a cerebral lesion to which it is functionally connected could contribute to initial NIHSS severity and explain the apparent dichotomy between patients \u0026lsquo;deficits and the hypo-perfused brain area. Diaschisis was first described by Von Monakow in 1914, to explain a functional impairment of a structurally normal areas as a result of remote, but connected lesion to the affected area.\u003csup\u003e9\u003c/sup\u003e Diaschisis is associated to a matched depression of blood flow and metabolism between the injured brain area and its connected counterparts.\u003csup\u003e10\u003c/sup\u003e In stroke, transhemispheric,\u003csup\u003e11,12\u003c/sup\u003e thalamic,\u003csup\u003e13\u003c/sup\u003e internal capsule\u003csup\u003e14,15\u003c/sup\u003e and cerebellar diaschisis\u003csup\u003e16\u0026ndash;18\u003c/sup\u003e have been described at both acute and chronic stages. Yet, the relation between diaschisis and initial stroke severity is seldom described. In anterior large vessel occlusion (LVO), the crossed cerebellar diaschisis (CCD) could likely contribute to LVO initial clinical deficit. Indeed, cerebello-cortical connectivity supports motor, cognitive and perceptual functions\u003csup\u003e19\u003c/sup\u003e thanks to reciprocal connections between the cerebellum, motor, parietal and prefrontal cortices.\u003csup\u003e20,21\u003c/sup\u003e Furthermore, CCD is associated to clinical impairments in both acquired and degenerative neurological diseases.\u003csup\u003e22\u0026ndash;24\u003c/sup\u003e After ischemic stroke, CCD has been reported in several studies using different techniques Single photon emission computerized tomography (SPECT),\u003csup\u003e22\u003c/sup\u003e Positron Emission Tomography (PET),\u003csup\u003e17,18\u003c/sup\u003e MRI perfusion imaging\u003csup\u003e25\u003c/sup\u003e and perfusion CT imaging (CTP)\u003csup\u003e16,26\u003c/sup\u003e with a prevalence ranging from 15%\u003csup\u003e25\u003c/sup\u003e to 58%.\u003csup\u003e17\u003c/sup\u003e The bulk of those studies focused on the relation between stroke volumes and CCD\u003csup\u003e26\u003c/sup\u003e or on stroke volumes and long term outcomes.\u003csup\u003e22,25,26\u003c/sup\u003eOnly one study focused on the role of CCD in acute stroke symptoms and its relation to admission NIHSS using \u003csup\u003e15\u003c/sup\u003eO-water brain PET on 19 patients. This study found a parallel improvement of CCD volume and NIHSS when serially and simultaneously assessed at admission, three and twenty-four hours post thrombolysis.\u003csup\u003e18\u003c/sup\u003e Yet, the results those studies must be balanced by the fact that they included proximal and distal vessel occlusion and were realized before mechanical thrombectomy was validated for LVO.\u003c/p\u003e\n\u003cp\u003eHere, we aim at determining, using CTP in a large cohort of anterior circulation LVO who underwent mechanical thrombectomy (MT), (i) the prevalence of CCD in acute anterior LVO, (ii) the part of the initial clinical deficit explained by CCD and (iii) the factors associated with the presence of a CCD using logistic regression models.\u0026nbsp;\u003c/p\u003e\n"},{"header":"Results","content":"\u003cp\u003e\u003cstrong\u003ea. Study population\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e296 patients benefited from MT in the period considered. 75 patients lacked CTP on admission, 34 patients had LVO in posterior circulation, intracranial stenosis or other abnormalities preventing interpretation and in 56 cases, CTP was judged either\u0026nbsp;incomplete or uninterpretable\u0026nbsp;preventing optimal evaluation of CCD. Finally, 131 patients were included (figure 1).\u003c/p\u003e\n\u003cp\u003eMain characteristics of the population are detailed in (table 1).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eb. CCD prevalence and characteristics\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNinety patients out of 131 (69%) had a CCD. Patients with CCD displayed significantly higher NIHSS on admission and at stroke discharge (17.90 \u0026plusmn; 6.1 vs 11.4\u0026plusmn;8.4, \u003cem\u003ep\u003c/em\u003e \u0026lt; 0.001; 9.6 \u0026plusmn; 7.7 vs 6.6 \u0026plusmn; 7.9, p = 0.049 respectively). Patients presenting with CCD had higher hypoperfusion volume (118.2 \u0026plusmn; 60.3 vs 69.3 \u0026plusmn; 59.7, \u003cem\u003ep\u0026nbsp;\u003c/em\u003e\u0026lt; 0.001).\u0026nbsp;Known atrial fibrillation (KAF) was present in 19 patients out of 87 (22%) in the CCD group while in 17 out of 41 patients (41%) without CCD (\u003cem\u003ep\u003c/em\u003e = 0.021). Other demographic and clinical data are illustrated in the Table 1. Figure 2. illustrates a typical CCD.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e--- Insert table 1 about here ---\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eLogistic regression model for the occurrence of a CCD\u0026nbsp;\u003c/em\u003e(table 2)\u003c/p\u003e\n\u003cp\u003eThe multiple linear regression model including age, NIHSS at admission, ischemic core volume, ischemic penumbra volume and known atrial fibrillation was statistically significant to predict the occurrence of a CCD treatment\u0026nbsp;(Nagelkerke determination coefficient,\u0026nbsp;R\u003csup\u003e2\u003c/sup\u003e = 0.366, \u0026chi;2 (degrees of freedom(dof):120, 38.4, \u003cem\u003ep\u003c/em\u003e \u0026lt; 0.001) and explained 37 % of CCD occurrence. In this model KAF independently accounted for 7% the outcome variability when age, hypoperfusion volume, core volume and NIHSS at admission were included in the null model as nuisance parameters.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e--- Insert table 2 ---\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eLinear regression model for admission NIHSS\u0026nbsp;\u003c/em\u003e(table 3)\u003c/p\u003e\n\u003cp\u003eThe multiple linear regression model including age, CCD, ischemic core volume, ischemic penumbra volume and known atrial fibrillation was statistically significant to predict admission NIHSS\u0026nbsp;(R\u003csup\u003e2\u003c/sup\u003e = 0.39, F (5 dof) 16,\u003cem\u003e\u0026nbsp;p\u003c/em\u003e \u0026lt; .001) and explained 39% of the variability of the admission NIHSS (R\u003csup\u003e2\u003c/sup\u003e = 0.39). In this model CCD independently accounted for 7% the outcome variability when age, hypoperfusion volume, core volume and KAF were included in the null model as nuisance parameters.\u003c/p\u003e\n\u003cp\u003e--- Insert table 3 about here ---\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eLinear regression model for NIHSS at stroke discharge\u0026nbsp;\u003c/em\u003e(table 4)\u003c/p\u003e\n\u003cp\u003eThe multiple linear regression model including age, NIHSS at admission, ischemic core volume, ischemic penumbra volume, known atrial fibrillation and CCD was statistically significant to predict NIHSS \u003cem\u003eat stroke discharge\u0026nbsp;\u003c/em\u003e(R\u003csup\u003e2\u003c/sup\u003e = 0.23, F (5 dof), 6, \u003cem\u003ep\u003c/em\u003e \u0026lt; .001) and explained 23% of the variability of the NIHSS 24 hours post-treatment (Nagelkerke determination coefficient, R\u003csup\u003e2\u003c/sup\u003e = 0.63). In this model CCD was not significantly associated to NIHSS at stroke discharge.\u003c/p\u003e\n\u003cp\u003e--- Insert table 4 about here ---\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eMain findings from this study are that (i) crossed cerebellar diaschisis occurs in 69 % of patients admitted for acute anterior LVO on CTP, (ii) CCD depends both on admission NIHSS score and hypo-perfused volume downstream of the LVO occlusion and shows an inverse relation with known atrial fibrillation and that (iii) CCD independently worsens admission NIHSS.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe findings of this study, albeit limited by its monocentric nature, are likely to be generalizable to other populations of LVO treated by thrombectomy. Indeed, our cohort matches closely the characteristics of the large published series on MT in LVO in terms of age, sex, admission NIHSS and rate of KAF.\u003csup\u003e8,38\u003c/sup\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eIn our cohort, a CCD was observed in 69% of all patients. This proportion parallels the seminal reports on CCD after hemispheric stroke using SPECT following \u003csup\u003e133\u003c/sup\u003eXe inhalation and \u003csup\u003e15\u003c/sup\u003eO-water brain PET where \u0026nbsp;CCD was found in 42%\u003csup\u003e39\u003c/sup\u003e and 58%\u003csup\u003e13\u003c/sup\u003e respectively. \u0026nbsp;However, the CCD rate, we report, is higher than in MRI perfusion weighting imaging (PWI) or MRI blood oxygenation-level dependent cerebrovascular reactivity (BOLD-CVR) where it was described between 15-44%,\u003csup\u003e25,40,41\u003c/sup\u003e and above the 35% described in the single cohort that used CTP.\u003csup\u003e16,26\u003c/sup\u003e The discrepancies between our study and previous works can be reduced to a common denominator. Indeed, CCD is proportional to the total volume of hemispheric hypo-perfusion,\u003csup\u003e18,22,26,39,42\u003c/sup\u003e a fact corroborated in our study. In the MRI studies, the hypoperfused volume was between 30%\u003csup\u003e40\u003c/sup\u003e and 50%\u003csup\u003e25\u003c/sup\u003e lower than in our cohort explaining the lower proportion of CCD. Differences in hypoperfusion volume fails, however, to explain why the rate of CCD was lower in the German study that also used CTP to detect CCD: hypoperfusion volume and admission NIHSS were of similar magnitude than in our study, reflecting comparable stroke severity. The lower rate of CCD in that cohort could reflect a selection bias relating to a \u003cem\u003epre-thrombectomy\u003c/em\u003e era, with patients included between 2009 and 2014.\u003csup\u003e16\u003c/sup\u003e Indeed, our population matches the clinical characteristics of the LVO population in the Thrombectomy trials and notably, in term of the 28% rate of KAF,\u003csup\u003e8\u003c/sup\u003e contrasting to the other cohort that used CTP had a population where patients had a 52% rate of KAF.\u003csup\u003e26\u003c/sup\u003e This difference in KAF prevalence may explain the lower rate of CCD they report, as we found in our cohort that KAF is significatively associated to lower likelihood of CCD. The relationship between KAF and CCD may relate to the onset of hypoperfusion: brutal in in cardioembolic stroke\u003csup\u003e43,44\u003c/sup\u003e and in more \u003cem\u003eprepared\u003c/em\u003e background in LVO due atherosclerotic disease where the LVO often occurs in a context of progressive narrowing of arterial lumen leading to previous relative hypoperfusion. CCD is a process triggered by cerebellar Purkinje cells deactivation from less corticopontine input. The Purkinje cell deactivation leads in turn to lower cerebellar metabolism and bloodflow,\u003csup\u003e45\u003c/sup\u003e a process that begins at the acute onset of LVO but is maximal after several hours.\u003csup\u003e46\u003c/sup\u003e The more progressive onset of hypoperfusion in LVO from non-cardioembolic origin would thus allow a more clear CCD as metabolic and blood flow changes in the cerebellum would have had more time to install.\u003c/p\u003e\n\u003cp\u003eIn our study, CCD accounts for 7% of admission NIHSS scores regardless of other factors such as penumbra or core volumes. Therefore, while not associated to a structural lesion, a CCD worsens the initial clinical picture of patients with CCD with by a component potentially fully reversible. The presence of CCD is probably an important parameter to consider for accurate analysis of recanalization therapies efficiency as well as acute functional prognosis. In Studies that assessed the benefit of MT +/- intravenous thrombolysis in anterior LVO, NIHSS improved from 17 to 5,\u003csup\u003e35,47\u003c/sup\u003e in which 10% of the improvement could reflect CCD resolution. This suggest that treatment efficiency studies should control for similar rates of CCD in intervention and non-interventions arms. Furthermore, initial clinical examination of patients suffering from LVO strokes should consider the possible interference caused by secondary cortico-cerebellar loops dysfunction added to LVO direct ischemic damage in cases of disproportionate clinical picture as compared to ischemic lesions.\u0026nbsp;\u003c/p\u003e"},{"header":"Conclusions","content":"\u003cp\u003eCrossed cerebellar diaschisis observed with CTP is a frequent phenomenon in anterior LVO strokes treated by MT. CCD is associated with higher stroke volumes and independently worsens admission NIHSS. CCD should be included in the interpretation of admission NIHSS and treatment efficiency, especially when there is a dichotomy between the expected deficit pertaining to the anterior LVO territory and the patient\u0026rsquo;s clinical presentation. Further studies are needed to evaluate the mechanisms and the implications of acute cerebellar dysfunction in and anterior LVO. \u003c/p\u003e"},{"header":"Material And Method ","content":"\u003cp\u003e\u003cstrong\u003ea. Study design and population\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003ePatients admitted between January 2017 and July 2021 were screened from our stroke registry at Erasmus Hospital in Brussels (Belgium) where all cases of acute ischemic strokes are recorded.\u003csup\u003e27,28\u003c/sup\u003e Inclusion criteria were patients (i) aged over eighteen years-old, (ii) presenting with an acute anterior LVO, defined as an occlusion of the ICA (T-type), MCA (M1 or M2 segments) and ACA (A1 or A2 segments) (iii) with a brain perfusion CT imaging with reliable analysis by Rapid\u0026reg; and SyngoVia\u0026reg; software and (iv) who underwent mechanical thrombectomy (MT).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eb. Cerebral perfusion imaging and CCD identification\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003ePre-MT imaging included non-contrast brain CT, CT brain/neck angiography and CT brain perfusion (CTP). Ischemic core was defined as brain volume with\u0026nbsp;cerebral blood flow (CBF) under 30% of the CBF of the homologous zone in the contralateral hemisphere. Ischemic penumbra was defined as brain volume with\u0026nbsp;time to maximum\u0026nbsp;(Tmax) contrast product arrival exceeded six seconds.\u003csup\u003e29\u003c/sup\u003e Those volume were automatically computed with Rapid\u0026reg; software.\u003csup\u003e30\u003c/sup\u003eAs Rapid\u0026reg; perfusion parameters thresholds may not be sensitive enough to identify a CCD, perfusion parameters were also analyzed using a qualitative approach with another software (Syngo.via\u0026reg;) approved in ischemic stroke management. The following perfusion parameters were assessed, mean transit time (MTT), Tmax, time to drain (TTD), time to peak (TTP), CBF and cerebral blood volume (CBV). CCD was defined as a decrease of CBF and CBV and/ or an increase MTT/ TTP/ TTD or T max parameters in the cerebellar hemisphere contralateral to the LVO, comparatively to the cerebellar hemisphere ipsilateral to the LVO. (figure 1) For subjects to be included, at least three consecutive CTP slices that encompassed the cerebellum were required. Imaging analysis was performed by two independent readers used to brain volume CTP interpretation. If a disagreement between readers occurred, results were discussed collegially.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e--- Insert figure 1 about here ---\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ec. Acute ischemic stroke care and functional outcomes\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAcute stroke management and care followed ESO guidelines and are detailed in.\u003csup\u003e27,31\u003c/sup\u003e MT recanalization was graded using the TICI scale.\u003csup\u003e32\u003c/sup\u003e Functional outcomes were evaluated by (i) the NIHSS score on admission and at stroke discharge.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eVariable definition, group comparisons and regression models\u003c/em\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u003c/p\u003e\n\u003cp\u003eVariable of interest were selected based on previous stroke outcome predictive models: Age,\u003csup\u003e33\u003c/sup\u003e NIHSS at admission,\u003csup\u003e7,34\u003c/sup\u003e ischemic core volume,\u003csup\u003e29\u003c/sup\u003e ischemic penumbra volume\u0026nbsp;\u003csup\u003e35,36\u003c/sup\u003e and known atrial fibrillation.\u003csup\u003e37\u003c/sup\u003e Those variables, as well as CCD, were chosen as covariates in a linear regression model to predict NIHSS on admission, NIHSS at stroke discharge and as covariates in a logistic regression model to predict a favourable stroke outcome at 90 days.\u0026nbsp;The relationship between variables/covariates and outcomes was assessed by Nagelkerke correlation coefficient. A value of p \u0026lt; 0.05 was considered statistically significant. Then, to assess the relative weight of CCD on outcome, the other variables were included in the \u003cem\u003enull model\u003c/em\u003e as nuisance parameters. A similar approach was used to build a logistic regression model to predict the occurrence of a CCD using the aforementioned variables of interest. Comparisons of selected interest variables between patients with and without CCD were done with a bilateral Student\u0026rsquo;s T-test.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;All statistical analysis was performed using Jasp\u0026reg; 16.0.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe study was reviewed and approved by the Ethics Committee of Erasmus Hospital, Brussels, Belgium. Written informed consent for participation was not required for this study in accordance with the national legislation and the institutional requirement. All methods were performed in accordance with the relevant guidelines and regulations.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAcknowledgement:\u0026nbsp;\u003c/strong\u003eFunding sources: Gilles Naeije is a Postdoctorate Clinical Master Specialists at the FRS-FNRS (Brussels, Belgium).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflict of Interest Statement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNo authors report no biomedical financial interests or potential conflicts of interest relating to this work.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eLN, AA, TN, NG:study design, data collection, analysis, manuscript writing.\u003c/p\u003e\n\u003cp\u003eSN: data collection, analysis.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData availability Statement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eData can be shared upon reasonable request to the corresponding author.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n \u003cli\u003e\u003cspan\u003eNational Institute of Neurological Disorders and Stroke rt-PA Stroke Study Group. 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Imaging\u003c/em\u003e \u003cstrong\u003e53\u003c/strong\u003e, 1190\u0026ndash;1197 (2021).\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003evon Bieberstein, L. \u003cem\u003eet al.\u003c/em\u003e Crossed Cerebellar Diaschisis Indicates Hemodynamic Compromise in Ischemic Stroke Patients. \u003cem\u003eTransl. Stroke Res.\u003c/em\u003e \u003cstrong\u003e12\u003c/strong\u003e, 39\u0026ndash;48 (2021).\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003eKamouchi, M., Fujishima, M., Saku, Y., Ibayashi, S. \u0026amp; Iida, M. Crossed cerebellar hypoperfusion in hyperacute ischemic stroke. \u003cem\u003eJ. Neurol. Sci.\u003c/em\u003e \u003cstrong\u003e225\u003c/strong\u003e, 65\u0026ndash;69 (2004).\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003eGuglielmi, V. \u003cem\u003eet al.\u003c/em\u003e Collateral Circulation and Outcome in Atherosclerotic Versus Cardioembolic Cerebral Large Vessel Occlusion. \u003cem\u003eStroke\u003c/em\u003e \u003cstrong\u003e50\u003c/strong\u003e, 3360\u0026ndash;3368 (2019).\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003eRebello, L. C. \u003cem\u003eet al.\u003c/em\u003e Stroke etiology and collaterals: atheroembolic strokes have greater collateral recruitment than cardioembolic strokes. \u003cem\u003eEur. J. Neurol.\u003c/em\u003e \u003cstrong\u003e24\u003c/strong\u003e, 762\u0026ndash;767 (2017).\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003eGold, L. \u0026amp; Lauritzen, M. Neuronal deactivation explains decreased cerebellar blood flow in response to focal cerebral ischemia or suppressed neocortical function. \u003cem\u003eProc. Natl. Acad. Sci. U. S. A.\u003c/em\u003e \u0026lt;bvertical-align:super;\u0026gt;99\u0026lt;/bvertical-align:super;\u0026gt;, 7699\u0026ndash;7704 (2002).\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003eDettmers, C. \u003cem\u003eet al.\u003c/em\u003e Contralateral cerebellar diaschisis 7 hours after MCA-occlusion in primates. \u003cem\u003eNeurol. Res.\u003c/em\u003e \u003cstrong\u003e17\u003c/strong\u003e, 109\u0026ndash;112 (1995).\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003eCampbell, B. C. V. \u003cem\u003eet al.\u003c/em\u003e Tenecteplase versus Alteplase before Thrombectomy for Ischemic Stroke. \u003cem\u003eN. Engl. J. Med.\u003c/em\u003e \u003cstrong\u003e378\u003c/strong\u003e, 1573\u0026ndash;1582 (2018).\u003c/span\u003e\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Tables","content":"\u003ctable border=\"0\" cellpadding=\"0\" cellspacing=\"0\" width=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"5\" width=\"100%\"\u003e\n \u003cp\u003e\u003cstrong\u003eTable 1.\u003c/strong\u003e Comparison of characteristics of acute ischemic stroke patients without CCD (CCD-) and with CCD (CCD+).\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"31.316187594553707%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"18.608169440242058%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eOverall (n=131)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.338880484114977%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eCDD (-) (n=41)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.239031770045386%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eCDD (+) (n=90)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.497730711043873%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003cem\u003ep\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"31.316187594553707%\"\u003e\n \u003cp\u003eAge\u0026nbsp;(mean \u0026plusmn; SD)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.608169440242058%\"\u003e\n \u003cp\u003e70.6\u0026nbsp;\u0026plusmn;\u0026nbsp;14.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.338880484114977%\"\u003e\n \u003cp\u003e71.1\u0026nbsp;\u0026plusmn;13.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.239031770045386%\"\u003e\n \u003cp\u003e70.4\u0026nbsp;\u0026plusmn;15.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.497730711043873%\"\u003e\n \u003cp\u003e0.80\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"31.316187594553707%\"\u003e\n \u003cp\u003eNIHSS\u003csub\u003eAdmission\u0026nbsp;\u003c/sub\u003e(mean \u0026plusmn; SD)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.608169440242058%\"\u003e\n \u003cp\u003e15.9\u0026nbsp;\u0026plusmn;7.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.338880484114977%\"\u003e\n \u003cp\u003e11.4\u0026plusmn;8.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.239031770045386%\"\u003e\n \u003cp\u003e17.90\u0026nbsp;\u0026plusmn;\u0026nbsp;6.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.497730711043873%\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0.001*\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"31.316187594553707%\"\u003e\n \u003cp\u003eNIHSS\u003csub\u003e\u0026nbsp;Discharge\u0026nbsp;\u003c/sub\u003e(mean \u0026plusmn; SD), n\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.608169440242058%\"\u003e\n \u003cp\u003e8.6\u0026nbsp;\u0026plusmn;\u0026nbsp;8.0 (117)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.338880484114977%\"\u003e\n \u003cp\u003e6.6\u0026nbsp;\u0026plusmn;\u0026nbsp;7.9 (38)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.239031770045386%\"\u003e\n \u003cp\u003e9.6\u0026nbsp;\u0026plusmn;\u0026nbsp;7.7(79)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.497730711043873%\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.049*\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"31.316187594553707%\"\u003e\n \u003cp\u003emRS 90 days \u0026le; 3 %, n\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.608169440242058%\"\u003e\n \u003cp\u003e41% (99)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.338880484114977%\"\u003e\n \u003cp\u003e48% (33)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.239031770045386%\"\u003e\n \u003cp\u003e38% (64)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.497730711043873%\"\u003e\n \u003cp\u003e0.332\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"31.316187594553707%\"\u003e\n \u003cp\u003eKnown AF (n, %)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.608169440242058%\"\u003e\n \u003cp\u003e128\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.338880484114977%\"\u003e\n \u003cp\u003e17 (41%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.239031770045386%\"\u003e\n \u003cp\u003e19 (22%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.497730711043873%\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.021*\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"31.316187594553707%\"\u003e\n \u003cp\u003eCore \u0026nbsp;volume (ml)\u0026nbsp;(mean \u0026plusmn; SD), n\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.608169440242058%\"\u003e\n \u003cp\u003e26.1\u0026nbsp;\u0026plusmn;\u0026nbsp;35.7 (129)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.338880484114977%\"\u003e\n \u003cp\u003e13.8\u0026nbsp;\u0026plusmn;\u0026nbsp;26.4 (40)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.239031770045386%\"\u003e\n \u003cp\u003e31.6\u0026nbsp;\u0026plusmn;\u0026nbsp;35.7 (89)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.497730711043873%\"\u003e\n \u003cp\u003e0.005\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"31.316187594553707%\"\u003e\n \u003cp\u003eHypoperfusion \u0026nbsp;volume (ml)\u0026nbsp;(mean \u0026plusmn; SD), n\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.608169440242058%\"\u003e\n \u003cp\u003e103.1\u0026nbsp;\u0026plusmn;\u0026nbsp;67.8 (129)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.338880484114977%\"\u003e\n \u003cp\u003e69.3\u0026nbsp;\u0026plusmn;\u0026nbsp;59.7(40)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.239031770045386%\"\u003e\n \u003cp\u003e118.2\u0026nbsp;\u0026plusmn;\u0026nbsp;60.3(89)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.497730711043873%\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0.001*\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e* Significant p-value. CCD-, no crossed cerebellar diaschisis; CCD+, presence of a crossed cerebellar diaschisis; SD, standard deviation; mRS, modified Rankin scale; AF, atrial fibrillation.\u0026nbsp;\u003c/p\u003e\n\u003ctable border=\"1\" cellpadding=\"0\" cellspacing=\"0\" width=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"4\" valign=\"top\" width=\"100%\"\u003e\n \u003cp\u003eTable 2. Linear regression coefficients for the variables assessed in the prediction model of CCD+.\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"28.73194221508828%\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003eVariables\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"18.13804173354735%\"\u003e\n \u003cp\u003e\u003cstrong\u003eOR\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"27.287319422150883%\"\u003e\n \u003cp\u003e\u003cstrong\u003e95% CI\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"25.84269662921348%\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003ep\u003c/em\u003e\u003c/strong\u003e\u003cstrong\u003e\u003cem\u003e-\u003c/em\u003e\u003c/strong\u003e\u003cstrong\u003evalue\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"28.73194221508828%\"\u003e\n \u003cp\u003eAge\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"18.13804173354735%\"\u003e\n \u003cp\u003e0.98\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"27.287319422150883%\"\u003e\n \u003cp\u003e0.94 - 1.01\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"25.84269662921348%\"\u003e\n \u003cp\u003e\u0026nbsp;0.17\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"28.73194221508828%\"\u003e\n \u003cp\u003ehypoperfusion volume\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"18.13804173354735%\"\u003e\n \u003cp\u003e1.01\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"27.287319422150883%\"\u003e\n \u003cp\u003e1.00- 1.02\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"25.84269662921348%\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.\u003c/strong\u003e\u003cstrong\u003e039*\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"28.73194221508828%\"\u003e\n \u003cp\u003eCore\u0026nbsp;volume\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"18.13804173354735%\"\u003e\n \u003cp\u003e0.99\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"27.287319422150883%\"\u003e\n \u003cp\u003e0.96- 1.02\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"25.84269662921348%\"\u003e\n \u003cp\u003e0.46\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"28.73194221508828%\"\u003e\n \u003cp\u003eKAF\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"18.13804173354735%\"\u003e\n \u003cp\u003e0.29\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"27.287319422150883%\"\u003e\n \u003cp\u003e0.11- 0.79\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"25.84269662921348%\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.015*\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"28.73194221508828%\"\u003e\n \u003cp\u003eNIHSS A\u003csub\u003edmission\u0026nbsp;\u003c/sub\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"18.13804173354735%\"\u003e\n \u003cp\u003e1.14\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"27.287319422150883%\"\u003e\n \u003cp\u003e1.06 - 1.23\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"25.84269662921348%\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt; 0.001*\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eCCD+, presence of a CCD; * Significant p-value. OR, Odd ratio; CI, confidence interval; KAF, known atrial fibrillation.\u003c/p\u003e\n\u003ctable border=\"1\" cellpadding=\"0\" cellspacing=\"0\" width=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"4\" valign=\"top\" width=\"100%\"\u003e\n \u003cp\u003eTable 3. Linear regression coefficients for the variables assessed in the prediction admission NIHSS.\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"30.56910569105691%\"\u003e\n \u003cp\u003e\u003cem\u003eVariables\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"20.16260162601626%\"\u003e\n \u003cp\u003e\u003cstrong\u003eCoefficient\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"23.089430894308943%\"\u003e\n \u003cp\u003e\u003cstrong\u003e95% CI\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"26.178861788617887%\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003ep\u003c/em\u003e\u003c/strong\u003e\u003cstrong\u003e\u003cem\u003e-\u003c/em\u003e\u003c/strong\u003e\u003cstrong\u003evalue\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"30.56910569105691%\"\u003e\n \u003cp\u003eAge\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"20.16260162601626%\"\u003e\n \u003cp\u003e0.147\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"23.089430894308943%\"\u003e\n \u003cp\u003e0.07- 0.22\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"26.178861788617887%\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt; 0.001*\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"30.56910569105691%\"\u003e\n \u003cp\u003eHypoperfusion volume\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"20.16260162601626%\"\u003e\n \u003cp\u003e0.026\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"23.089430894308943%\"\u003e\n \u003cp\u003e0.01- 0.05\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"26.178861788617887%\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.02*\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"30.56910569105691%\"\u003e\n \u003cp\u003eCore\u0026nbsp;volume\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"20.16260162601626%\"\u003e\n \u003cp\u003e0.014\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"23.089430894308943%\"\u003e\n \u003cp\u003e-0.04 - 0.07\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"26.178861788617887%\"\u003e\n \u003cp\u003e0.625\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"30.56910569105691%\"\u003e\n \u003cp\u003eKAF\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"20.16260162601626%\"\u003e\n \u003cp\u003e1.173\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"23.089430894308943%\"\u003e\n \u003cp\u003e-1.25- 3.60\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"26.178861788617887%\"\u003e\n \u003cp\u003e0.34\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"30.56910569105691%\"\u003e\n \u003cp\u003eCCD+\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"20.16260162601626%\"\u003e\n \u003cp\u003e4.85\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"23.089430894308943%\"\u003e\n \u003cp\u003e2.37- 7.33\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"26.178861788617887%\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt; 0.001*\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e* Significant p-value. CI, confidence interval; V, volume; KAF, known atrial fibrillation; CCD+, presence of a crossed cerebellar diaschisis.\u003c/p\u003e\n\u003ctable border=\"1\" cellpadding=\"0\" cellspacing=\"0\" width=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"4\" valign=\"top\" width=\"100%\"\u003e\n \u003cp\u003eTable 4. Linear regression coefficients for the variables assessed in the prediction model of stroke discharge NIHSS.\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"30.73170731707317%\"\u003e\n \u003cp\u003e\u003cem\u003eVariables\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"20%\"\u003e\n \u003cp\u003e\u003cstrong\u003eCoefficient\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"23.089430894308943%\"\u003e\n \u003cp\u003e\u003cstrong\u003e95% CI\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"26.178861788617887%\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003ep\u003c/em\u003e\u003c/strong\u003e\u003cstrong\u003e\u003cem\u003e-\u003c/em\u003e\u003c/strong\u003e\u003cstrong\u003evalue\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"30.73170731707317%\"\u003e\n \u003cp\u003eAge\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"20%\"\u003e\n \u003cp\u003e0.14\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"23.089430894308943%\"\u003e\n \u003cp\u003e0.05- 0.24\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"26.178861788617887%\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;0.004*\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"30.73170731707317%\"\u003e\n \u003cp\u003eHypoperfusion volume\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"20%\"\u003e\n \u003cp\u003e0.01\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"23.089430894308943%\"\u003e\n \u003cp\u003e-0.02 -0.03\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"26.178861788617887%\"\u003e\n \u003cp\u003e0.750\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"30.73170731707317%\"\u003e\n \u003cp\u003eCore\u0026nbsp;volume\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"20%\"\u003e\n \u003cp\u003e0.09\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"23.089430894308943%\"\u003e\n \u003cp\u003e0.02 - 0.16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"26.178861788617887%\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.017*\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"30.73170731707317%\"\u003e\n \u003cp\u003eKAF\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"20%\"\u003e\n \u003cp\u003e-0.24\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"23.089430894308943%\"\u003e\n \u003cp\u003e-3.31 - 2.82\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"26.178861788617887%\"\u003e\n \u003cp\u003e0.875\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"30.73170731707317%\"\u003e\n \u003cp\u003eCCD+\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"20%\"\u003e\n \u003cp\u003e2.01\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"23.089430894308943%\"\u003e\n \u003cp\u003e-1.11 - 5.12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"26.178861788617887%\"\u003e\n \u003cp\u003e0.204\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e* Significant p-value. CI, confidence interval; V, volume; KAF, known atrial fibrillation; CCD+, presence of a crossed cerebellar diaschisis.\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"NIHSS, Large vessel occlusion, Crossed cerebellar diaschisis, Perfusion, stroke outcome \u0026 thrombectomy","lastPublishedDoi":"10.21203/rs.3.rs-1821086/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-1821086/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground and Purpose \u003c/strong\u003e\u003c/p\u003e\u003cp\u003eInitial NIHSS in anterior large vessel occlusion (LVO) correlates partially with the hypoperfusion volume. We aimed at assessing the contribution of crossed cerebellar diaschisis (CCD) from the hypo-perfused territory on LVO initial clinical deficit.\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eMethod\u003c/strong\u003e\u003c/p\u003e\u003cp\u003eCCD was retrospectively identified by brain CT perfusion imaging (CTP) in patients with anterior LVO treated by mechanical thrombectomy (MT) from January 2017 to July 2021. CCD was defined by CTP parameters alteration in contralateral cerebellar hemisphere to the LVO. NIHSS, clinical/perfusion variables and CCD were included in regression models to assess their inter-relationships.\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eResults\u003c/strong\u003e\u003c/p\u003e\u003cp\u003e206 patients were included. CCD was present in 90 patients (69%). NIHSS scores were higher on admission and at stroke discharge among patients with CCD (17.90 ± 6.1vs 11.4 ± 8.4, p \u0026lt;0.001; 9.6 ± 7.7 vs 6.6 ± 7.9, p = 0.049 respectively). Patients with a CCD had higher stroke volumes (118.2 ± 60.3 vs 69.3 ± 59.7, p\u0026lt;0.001) and lower rate of known atrial fibrillation (22 % vs 41%, p = 0.021). On multivariable logistic regression, CCD independently worsened initial NIHSS (OR 4.85 (2.37-7.33); p\u0026lt;0.001).\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eConclusion\u003c/strong\u003e\u003c/p\u003e\u003cp\u003eCCD is found in 69% of LVO on admission CTP, correlates with stroke volumes and independently worsens initial NIHSS.\u003c/p\u003e","manuscriptTitle":"Crossed cerebellar diaschisis worsens the clinical presentation in acute large vessel occlusion","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2022-07-15 17:58:38","doi":"10.21203/rs.3.rs-1821086/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"77a41c39-7cb4-49db-8a99-0b863dfa4d10","owner":[],"postedDate":"July 15th, 2022","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2022-10-12T03:29:09+00:00","versionOfRecord":[],"versionCreatedAt":"2022-07-15 17:58:38","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-1821086","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-1821086","identity":"rs-1821086","version":["v1"]},"buildId":"7rjqhiLT3MXkJMwkYKINL","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}