We identified four independent predictors of MCE in this study, The three of which were consistent with previous studies, including NIHSS, MLS and ACA territory involvement(19, 20). The association between KAF and MCE are still controversial. On this basis we present a visual MANA (MLS, ACA territory involvement and KAF) nomogram to assess risk for development of MCE in Chinese patients with LHI. The c-statistic of MANA nomogram up to 0.887 ± 0.041 and AUC-ROC value in this cohort was 0.887 (95%CI, 0.828~0.934).
For the past few years, with the development of cardiac monitoring technologies, physicians have noticed atrial fibrillation (AF) after ischemic stroke or transient ischemic attack (TIA). About 23.7% patients without AF before the stroke later develop AF(21), termed AF detected after stroke (AFDAS). Nevertheless, the relationship between KAF and MCE has never been reported. Currently, the KAF is considered as the cardiogenic AF, which was mainly caused by cardiac remodeling, while AF detected after stroke (AFDAS) may composed of multiple types of AF, including the preexisting but newly diagnosed atrial fibrillation (cardiogenic AF) and newly emerged atrial fibrillation (neurogenic AF)(22). The neurogenic AF is the main type of AFDAS, which may be caused by inflammatory response and dysfunction of the autonomic regulation of cardiac rhythm(22, 23). Based on this difference between mechanisms of KAF and AFDAS, the effect of AFDAS on stroke severity may also vary from that of KAF. Previous research has found that stroke patients with KAF have higher rate of death or stroke recurrence (including hemorrhagic and ischemic stroke) than patients with AFDAS, but the difference was unadjusted(23). In order to verify this supposition, we set up another multivariable regression to assess the differences in the risk of MCE among the SR, AFDAS and KAF (Table 3). After adjusting for confounders, we found that compared to patients with sinus rhythm (SR) or AFDAS, patients with KAF had significantly higher risk of MCE (adjusted OR 4.29, 95%CI, 1.28~14.36). However, the risk between SR and AFDAS had no significant difference. One possible reason is that patients with KAF had more severe hypoperfusion, which lead to greater infarct growth and larger infarcts(24). Our research also suggests that patients with KAF may have more severe stroke than patients with AFDAS (mean NIHSS 20 vs 18 & mean infarct volume 231.1mL vs 191.5mL). Additionally, it is noticeable that the risk factors of cardiac remodeling, such as endothelin-1 and matrix metalloproteinase, are also associated with brain edema(25-28). Furthermore, neurogenic AF as the “functional AF”, may have less AF burden than cardiogenic AF, which can also influence the prognosis of patients(29). It’s also worth noting that only 2.7% patients with AF in China received anticoagulant treatment(30), which may also associated with the more severe ischemic stroke and brain edema.
For patients with LHI, ACA territory involvement often hints the existence of larger infarction or more proximal vascular occlusion (such as the carotid T occlusion or ICA occlusion), less hemispheric collateral flow and greater volume of edematous brain tissue(31). The NIHSS score is correlated with stroke severity and infarct volume(10, 32), and MLS is a visual indicator on CT or MRI images, even Sonographic monitoring, for assessing severity of brain edema(33, 34). Previous study enrolled NHISS and MLS as categorical variables into scoring models of malignant brain edema for the convenience of clinical use(10, 20). However, compared to continuous use of NIHSS and MLS, the categorical use will lose some precision. Although the nomogram can get rid of that limitation, its practicability is less than scoring models. To make up for these deficiencies, we establish a web operation interface (http://www.MANA-nom.com) for MANA nomogram, which combines practicality and accuracy. Additionally, we did not collect data from CTA, DWI or special measurement techniques(19, 35-37), considering the model needed to be available and propagable.
Unlike previous nomogram that only roughly calculate an approximation, the dynamic MANA nomogram can provide an exact value. Furthermore, it's convenient for neurologists all over the world. After entering a patient’s NIHSS, MLS, infarct area (ACA territory or not) and KAF (Yes or No) on http://www.MANA-nom.com, the neurologist can get the patient’s corresponding probability of developing MCE. Furthermore, the MANA nomogram can also be used to identify patients who need early surgical treatment, or to aid in establishing of reasonable decisions for patients with immense likelihood of MCE of LHI.