We identified four independent MCE predictors in this study, Three of which consistent with previous studies, including NIHSS, MLS and ACA territory involvement(17, 18). However the association between KAF and MCE is still controversial. On this basis we developed a visual MANA (MLS, ACA territory involvement and KAF) nomogram to assess the risk of MCE development of MCE in Chinese patients with LHI. The c-statistic of the MANA nomogram was up to 0.887 ± 0.041 while the AUC-ROC 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 stroke later develop AF(23), termed AF detected after stroke (AFDAS). Nevertheless, the relationship between KAF and MCE has never been clarified. Currently, KAF is considered as the cardiogenic AF, which was mainly caused by cardiac remodeling, while AF detected after stroke (AFDAS) may be composed of multiple AF types, including preexisting but newly diagnosed atrial fibrillation (cardiogenic AF) and newly emerged atrial fibrillation (neurogenic AF)(24). Neurogenic AF is the main type of AFDAS, which may be caused by the inflammatory response and dysfunction of the autonomic regulation of the cardiac rhythm(24, 25). Based on this mechanistic difference between KAF and AFDAS, the effect of AFDAS on stroke severity may also vary from that of KAF. Previous research found that stroke patients with KAF have a higher rate of death or stroke recurrence (including hemorrhagic and ischemic stroke) than patients with AFDAS, but the difference was unadjusted(25). To verify this supposition, we set up another multivariable regression to assess the differences in MCE risk among the sinus rhythm (SR), AFDAS and KAF (Table 3). After adjusting for confounders, we found that compared to patients with 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 did not significantly differ. One possible reason is that patients with KAF had more severe hypoperfusion, leading to greater infarct growth and larger infarcts(26). 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 risk factors of cardiac remodeling, such as endothelin-1 and matrix metalloproteinase, are also associated with brain edema(27-30). Furthermore, neurogenic AF as “functional AF”, may have less AF burden than cardiogenic AF, which can also influence patient prognosis(31). It is also worth noting that only 2.7% patients with AF in China received anticoagulant treatment(32), which may also be associated with the more severe ischemic stroke and brain edema incidence in China.
For patients with LHI, ACA territory involvement often hints the existence of larger infarction or more proximal vascular occlusion, such as carotid T or internal carotid artery (ICA) occlusion, less hemispheric collateral flow and greater volume of edematous brain tissue(15). Further, the NIHSS score is correlated with stroke severity and infarct volume(10, 33), and MLS is a visual indicator on CT or MRI images, even sonographic monitoring, for assessing the severity of brain edema(34, 35). Previous studies included NHISS and MLS as categorical variables into scoring models of malignant brain edema for the convenience of clinical use(10, 18). However, compared to the continuous use of NIHSS and MLS, the categorical use loses precision. Despite the nomogram being able to circumvent that limitation, it has lesser practicability than scoring models. To make up for these deficiencies, we established a web operation interface (http://www.MANA-nom.com) for the MANA nomogram, which combines practicality and accuracy. Additionally, we did not collect data from CT angiography (CTA), DWI or special measurement techniques(17, 36-38), considering that the model needed to be available and propagable.
Unlike previous nomograms that 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. The MANA nomogram can also be used to identify patients who need early surgical treatment, or aid in the decision-making process for patients with high likelihood of MCE of LHI.